СТРЕС-ІНДУКОВАНІ ЗМІНИ СТАТУСУ МЕТИЛЮВАННЯ ГЕНІВ Mmp1 ТА Mmp8 У ПУХЛИННІЙ ТКАНИНІ ЩУРІВ З КАРЦИНОМОЮ ГЕРЕНА
Background. Chronic stress is a key determinant of public health, signifi  antly impacting regulatory systems and potentially contributing to carcinogenesis. Chronic stress, through the activation of the hypothalamic-pituitary- adrenal axis and glucocorticoid signaling, can modify the e...
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Experimental Oncology| _version_ | 1868022653007167488 |
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| author | Borikun, T. Herasymchuk, Y. |
| author_facet | Borikun, T. Herasymchuk, Y. |
| author_institution_txt_mv | [
{
"author": "T. Borikun",
"institution": "R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, the National Academy of Sciences of Ukraine, Kyiv, Ukraine"
},
{
"author": "Y. Herasymchuk",
"institution": "Educational and Scientific Centre «Institute of Biology and Medicine» of Taras Shevchenko National University of Kyiv , Kyiv, Ukraine"
}
] |
| author_sort | Borikun, T. |
| baseUrl_str | https://exp-oncology.com.ua/index.php/Exp/oai |
| collection | OJS |
| datestamp_date | 2026-06-14T20:08:50Z |
| description | Background. Chronic stress is a key determinant of public health, signifi  antly impacting regulatory systems and potentially contributing to carcinogenesis. Chronic stress, through the activation of the hypothalamic-pituitary- adrenal axis and glucocorticoid signaling, can modify the epigenetic landscape of cells, including DNA meth- ylation. Th s study aimed to evaluate whether chronic glucocorticoid-induced stress modulates the methylation status of the promoter regions of the Mmp1 and Mmp8 genes in the tumor tissue of rats with Guerin carcinoma. Materials and Methods. to simulate chronic stress, dexamethasone (DEX) was administered subcutaneously to laboratory rats with transplanted Guerin carcinoma. tumor samples were collected on days 7, 14, and 21 of tumor growth. The methylation status of the Mmp1 and Mmp8 gene promoters was analyzed using methylation-specifi PCR. The level of methylation was quantifi  d as the ratio of methylated to unmethylated PCR products, expressed as a percentage. Results. In the control group (Guerin carcinoma without DEX), the Mmp1 promoter was hypo- methylated (38—40% methylation) throughout the observation period. DEX administration led to a further slight decrease in Mmp1 methylation to 32%, though insignifi  ant. In contrast, the Mmp8 promoter in tumor tissue showed baseline methylation levels of 55—57%. Under the influence of DEX, Mmp8 hypermethylation was ob- served as early as day 7 (61%) and signifi  antly progressed by day 14 (67%) and day 21 (69%). Conclusion. Our study demonstrated that chronic glucocorticoid-induced stress altered the epigenetic profile of tumor cells by in- ducing differential methylation of the matrix metalloproteinase genes. Specifi  ally, it promoted the maintenance of Mmp1 hypomethylation and signifi  antly increased the Mmp8 promoter hypermethylation. These fi  dings suggest that chronic stress may contribute to an aggressive tumor phenotype through the epigenetic regulation of extracel- lular matrix remodeling. |
| doi_str_mv | 10.15407/exp-oncology.2026.01.046 |
| first_indexed | 2026-06-15T01:00:26Z |
| format | Article |
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46 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
SHORT COMMUNICATION
C i t a t i o n: Borikun T, Herasymchuk Y. Stress-induced changes in the methylation status of Mmp1 and Mmp8 genes in
tumor tissue of rats with Guerin carcinoma. Exp Oncol. 2026; 48(1): 46-50. https://doi.org/10.15407/exp-oncology.
2026.01.046
© PH “Akademperiodyka” of the NAS of Ukraine, 2026. This is an open access article under the CC BY-NC-ND license
(https://creativecommons.org/licenses/by-nc-nd/4.0/)
https://doi.org/10.15407/exp-oncology.2026.01.046
T. Borikun 1, *, Y. Herasymchuk 2
1 R.E. Kavetsky Institute of Experimental Pathology, Oncology
and Radiobiology, the National Academy of Sciences of Ukraine, Kyiv, Ukraine
2 Educational and Scientific Centre «Institute of Biology and Medicine»
of Taras Shevchenko National University of Kyiv , Kyiv, Ukraine
* Correspondence: E-mail: tborikun@gmail.com
Stress-Induced Changes in the Methylation
Status of Mmp1 and Mmp8 Genes in Tumor
Tissue of Rats with Guerin Carcinoma
Background. Chronic stress is a key determinant of public health, significantly impacting regulatory systems and
potentially contributing to carcinogenesis. Chronic stress, through the activation of the hypothalamic-pituitary-
adrenal axis and glucocorticoid signaling, can modify the epigenetic landscape of cells, including DNA meth-
ylation. This study aimed to evaluate whether chronic glucocorticoid-induced stress modulates the methylation
status of the promoter regions of the Mmp1 and Mmp8 genes in the tumor tissue of rats with Guerin carcinoma.
Materials and Methods. To simulate chronic stress, dexamethasone (DEX) was administered subcutaneously to
laboratory rats with transplanted Guerin carcinoma. Tumor samples were collected on days 7, 14, and 21 of tumor
growth. The methylation status of the Mmp1 and Mmp8 gene promoters was analyzed using methylation-specific
PCR. The level of methylation was quantified as the ratio of methylated to unmethylated PCR products, expressed
as a percentage. Results. In the control group (Guerin carcinoma without DEX), the Mmp1 promoter was hypo-
methylated (38—40% methylation) throughout the observation period. DEX administration led to a further slight
decrease in Mmp1 methylation to 32%, though insignificant. In contrast, the Mmp8 promoter in tumor tissue
showed baseline methylation levels of 55—57%. Under the influence of DEX, Mmp8 hypermethylation was ob-
served as early as day 7 (61%) and significantly progressed by day 14 (67%) and day 21 (69%). Conclusion. Our
study demonstrated that chronic glucocorticoid-induced stress altered the epigenetic profile of tumor cells by in-
ducing differential methylation of the matrix metalloproteinase genes. Specifically, it promoted the maintenance of
Mmp1 hypomethylation and significantly increased the Mmp8 promoter hypermethylation. These findings suggest
that chronic stress may contribute to an aggressive tumor phenotype through the epigenetic regulation of extracel-
lular matrix remodeling.
Keywords: DNA methylation, chronic stress, cancer.
Chronic stress poses a major issue in the current po
pulation and is acknowledged as a crucial factor in
public health. Global epidemiological research indi-
cates that approximately 35% of adults consistently
report feeling stressed, and this pattern is steadily ri
sing [1, 2]. Considering the ongoing geopolitical situ-
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 47
Stress-Induced Changes in the Methylation Status of Mmp1 and Mmp8 Genes in Tumor Tissue of Rats
ation in Ukraine, this issue impacts the whole popula-
tion and should be seen as a major factor in public
health challenges.
In this regard, chronic stress is considered an im-
portant modifier of the functioning of regulatory
systems. The prolonged activation of neuroendo-
crine mechanisms, in particular the hypothalam-
ic-pituitary-adrenal (HPA) axis, is accompanied by
increased secretion of glucocorticoids and cate-
cholamines, which can lead to the disruption of cel-
lular homeostasis, changes in the immune re-
sponse, and the creation of conditions favorable for
the development of pathological processes, includ-
ing carcinogenesis. Glucocorticoid-dependent sig-
naling can affect DNA methyltransferase activity
and chromatin remodeling, which leads to stable
changes in the epigenetic landscape of cells [3].
The accumulated experimental and clinical data
indicate that chronic stress is associated with an in-
creased risk of the occurrence and progression of ma-
lignant neoplasms. This is due, in particular, to the
influence of stress-induced hormones on the process-
es of proliferation, apoptosis, angiogenesis, and inva-
sion of tumor cells. The epigenetic mechanisms play
an important role in the implementation of these ef-
fects, among which DNA methylation is one of the
key regulators of gene expression. The changes in
methylation of the promoter regions can lead to the
activation of oncogenes or suppression of tumor sup-
pressor genes, thereby contributing to malignant
transformation of cells [4, 5].
Of particular interest are the genes of the matrix
metalloproteinase family, MMP1 and MMP8,
whose products are involved in the degradation of
extracellular matrix components and tumor cell in-
vasion [6]. It was shown that the increased expres-
sion of MMP1 is associated with tumor progression
and decreased survival in xenograft animal mo
dels [7]. The role of MMP8 in cancer is more com-
plex and context-dependent, since, along with par-
ticipation in matrix degradation, this enzyme can
exhibit both pro- and antitumor properties [8].
The MMP family gene expression is regulated at
various levels, including epigenetic mechanisms,
among which DNA methylation plays an important
role. It has been shown that the level of methylation
of the MMP promoter regions is inversely related to
MMP expression and invasive potential of cells [9].
Despite the available data on the role of stress and
epigenetic changes in carcinogenesis, it remains un-
clear how chronic stress modulates the methylation
of specific genes involved in extracellular matrix deg-
radation, in particular MMP1 and MMP8. Thus, we
aimed to evaluate whether chronic glucocorticoid-in-
duced stress modulates the methylation status of the
promoter regions of the Mmp1 and Mmp8 genes in
the tumor tissue of rats with Guerin carcinoma.
Materials and Methods
Animal model. The study was conducted on male
Wistar rats aged 2.5 months and weighing 180–200 g.
The animals were provided by the vivarium of the
R.E. Kavetsky Institute of Experimental Pathology,
Oncology and Radiobiology of the National Acad-
emy of Sciences of Ukraine. During the study, the
animals were kept in standard vivarium conditions
with natural lighting, on a full diet with free access
to food and water. The study was conducted in ac-
cordance with the standard international rules on
biological ethics and the European Convention for
the Protection of Vertebrate Animals Used for Ex-
perimental and Other Scientific Purposes. All ani-
mals underwent a 10-day quarantine before being
included in the study. After the adaptation period,
the animals were weighed, divided into groups, and
marked by serial number. As a model of tumor
growth, Guerin carcinoma was used, obtained from
the Bank of Cell Lines from Human and Animal
Tissues of the IEPOR NASU.
A suspension of Guerin carcinoma cells in saline
was transplanted (106 cells per animal) subcutane-
ously to the right side, closer to the back. The animals
were divided into groups of 5 animals each. The ani
mals of the experimental group were injected with
0.5 mL of dexamethasone (dexamethasone solu
tion for intravenous use 4 mg/mL, PJSC «Lekhim-
Kharkiv», Kharkiv, Ukraine) at a concentration of
0.5 mg/kg, subcutaneously starting from day 2 after
Guerin carcinoma inoculation every other day for
12 days. The solutions were administered using a
U-40 BD Micro-Fine Plus 30G microinjection insu-
lin syringe (Becton, Dickinson and Company, USA).
The animals were slaughtered on days 7, 14, and 21
after the start of the experiment.
Methylation-specific real-time PCR. Genomic
DNA from frozen tumor tissue was isolated using
a commercial DNA/RNA-Mag reagent kit (Xema,
Ukraine) and treated with sodium bisulfite accor
ding to the manufacturer’s instructions.
48 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
T. Borikun, Y. Herasymchuk
The amount of isolated DNA was determined
using a NanoDrop 2000c Spectrophotometer
(ThermoScientific, USA). The purity of the isolated
DNA was monitored by the ratio of optical absorp-
tion values at wavelengths of 260 and 280 nm. The
DNA was stored at –20 °C before use.
For real-time PCR, the sequences of the primers
were obtained from the resource https://www.ncbi.
nlm.nih.gov/tools/primer-blast and synthesized by
Metabion, Germany (Table) using the commercial
EpiTect MethyLight PCR +ROX Vial Kit (QIAGEN
GmbH, Germany). They were used according to
the manufacturer’s protocol.
After standardization of methylated (M) and un-
methylated (U) PCR products by the 2–ΔCt method,
methylation percent was calculated as M/(M + U),
which indicated the levels of gene methylation.
Statistical methods. Statistical processing of the
obtained results was carried out using the STATIS-
TICA 6.0 program (Statistica Inc., USA). The stan-
dard descriptive, parametric, and non-parametric
statistical methods were used. The significance of
the differences between the mean values was as-
sessed using Student’s t-test (for a parametric dis-
tribution) or the Mann — Whitney U-test (for a
non-parametric distribution). Differences at p ≤
≤ 0.05 were considered significant.
Results and Discussion
The features of methylation of the promoter region
of the Mmp1 and Mmp8 genes in tumor tissue of
rats with Guerin carcinoma were studied. It was
found that the MMP1 gene promoter was hypo-
methylated on day 7 after transplantation (the ratio
of methylated PCR products to unmethylated ones
was 39%). From day 7 to day 21 of tumor growth,
this ratio did not significantly change and fluctu-
ated within 38—40% (Figure).
Dexamethasone (DEX) also caused a slight de-
crease in the level of methylation of the MMP1
gene promoter (up to 32%); however, insignificant
compared to the control. Genevay et al. [10] men-
tioned in their study that DEX can inhibit MMP1
Primers used in the study
Gene Methylation status Primer
Mmp1 Methylated Forward 5′-ATTTTAAA TAAGATGTGTGCG-3′
Methylated Reverse 5′-AACCATCA AAACCAATCTTTT-3′
Unmethylated Forward 5′-ATTTTAAA TAAGATGTGTGTG-3′
Unmethylated Reverse 5′-AACCATCA AAACCAATCTTTT-3′
Mmp8 Methylated Forward 5′-TTGTAGAC GTGAGTTATCGTATTCG-3′
Methylated Reverse 5′-AATCGTAA AAACCTAACCCTAACG-3′
Unmethylated Forward 5′-TGTAGATG TGAGTTATTGTATTTGG-3′
Unmethylated Reverse 5′-ATCATAAAA ACCTAACCCTAACAA-3′
The degree of methylation of the promoter regions of the Mmp1 and Mmp8 genes in tumor tissue of rats with Guerin
carcinoma. * p < 0.05 compared to control
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 49
Stress-Induced Changes in the Methylation Status of Mmp1 and Mmp8 Genes in Tumor Tissue of Rats
activity, which is probably due to its effect on the
glucocorticoid-dependent signaling pathways.
When studying the methylation status of the
Mmp8 gene promoter, we found that in Guerin car-
cinoma tissue, it was slightly hypermethylated (55%
of methylated sites on days 7 and 14 of tumor growth
and 57% on day 21). In the tumor tissue of
DEX-treated rats, the Mmp8 gene promoter showed
increased hypermethylation above control levels by
day 7 (61% of methylated sites), with this trend per-
sisting over time. Our data were consistent with the
results of current molecular genetic studies, which
identify MMP8 as one of the most stress-sensitive
genes. In particular, Daskalakis et al. [11] have
shown that MMP8 is among the key genes whose
expression is significantly altered by exposure to
traumatic events and is regulated by glucocorticoids.
The progressive hypermethylation of the promoter
under the action of DEX, which we have identified,
may be an epigenetic mechanism leading to reduced
expression of this gene, similar to what is observed
in stress-induced conditions in other models.
To simulate chronic stress conditions in labora-
tory animals, we used DEX administered subcuta-
neously. DEX, a synthetic glucocorticoid receptor
agonist, is widely used as a pharmacological model
of stress, and its long-term administration mimics
the activation of the HPA axis [12].
Glucocorticoids, in particular DEX, are able to
modulate the epigenetic state of cells, namely DNA
methylation, which is a key mechanism for the
long-term regulation of gene expression. Activation
of glucocorticoid receptors causes interaction with
regulatory regions of the genome and the recruit-
ment of epigenetic modification enzymes, such as
DNA methyltransferases, which leads to chromatin
remodeling and changes in DNA accessibility to
transcription factors. Experimental studies show
that administration of DEX can induce both local
and genome-wide methylation changes, including
differential methylation of CpG sites in genes in-
volved in metabolic and signaling pathways, most-
ly hypomethylation [13—15].
Methylation of the promoter regions of the
MMP1 and MMP8 genes is one of the key mecha-
nisms of epigenetic regulation of their expression,
which determines the level of transcription and
functional activity of these enzymes in cells. For
MMP1, experimental data show that hypomethy
lation of the promoter region is associated with a
significant increase in the expression of the en-
zyme, which contributes to the active degradation
of collagen types I and III, increased invasiveness,
and metastatic potential of tumor cells [16].
In the case of MMP8, methylation changes are
more differentiated: in some tumor contexts, hy-
pomethylation is observed, which increases the ex-
pression of the enzyme, enhancing inflammatory
and remodeling processes, while in other cases, hy-
permethylation occurs, which reduces the antitu-
mor activity of MMP8 and may contribute to the
loss of its protective function [9].
To sum up, our study confirmed the effective-
ness of using DEX as a relevant pharmacological
model of chronic stress for studying epigenetic
modifications in tumor tissue. The key result of the
work is the identification of a differential effect of
stress on the methylation of the Mmp1 and Mmp8
genes. The simulated chronic stress contributed to
the formation of an aggressive epigenetic profile of
the tumor, enhancing the imbalance in the metal-
loproteinase system.
Funding
This study was supported by the Research Program
“Development of Technology for Identifying Stress-
Induced Factors of Initiation of Metastatic Bone
Lesions” (No. 0125U000655) funded by the Nation-
al Academy of Sciences of Ukraine.
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12. Bassil K, De Nijs L, Rutten BPF, et al. In vitro modeling of glucocorticoid mechanisms in stress-related mental dis-
orders: current challenges and future perspectives. Front Cell Dev Biol. 2022;10:1046357. https://doi.org/10.3389/
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13. Li Y, Cai HY, Liu GH, et al. Effects of stress simulated by dexamethasone on jejunal glucose transport in broilers.
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cers14051232
Submitted: March 01, 2026
Т. Борікун 1, Є. Герасимчук 2
1 Інститут експериментальної патології, онкології та радіобіології
ім. Р.Є. Кавецького Національної академії наук України, Київ, Україна
2 Навчально-науковий центр «Інститут біології та медицини»
Київського національного університету імені Тараса Шевченка, Київ, Україна
СТРЕС-ІНДУКОВАНІ ЗМІНИ СТАТУСУ МЕТИЛЮВАННЯ ГЕНІВ Mmp1
ТА Mmp8 У ПУХЛИННІЙ ТКАНИНІ ЩУРІВ З КАРЦИНОМОЮ ГЕРЕНА
Стан питання. Хронічний стрес є ключовим фактором громадського здоров›я, який суттєво впливає на ре-
гуляторні системи та потенційно сприяє канцерогенезу. Хронічний стрес, через активацію гіпоталамо-гіпо-
фізарно-надниркової осі та глюкокортикоїдної сигналізації, може змінювати епігенетичний ландшафт клітин,
включаючи метилювання ДНК. Метою даного дослідження було оцінити, чи хронічний стрес, викликаний
глюкокортикоїдами, модулює метилювання промоторних ділянок генів Mmp1 та Mmp8 у пухлинній тканині
щурів з карциномою Герена. Матеріали та методи. Для моделювання хронічного стресу лабораторним щу-
рам з трансплантованою карциномою Герена вводили дексаметазон підшкірно. Зразки пухлини збирали на
7, 14 та 21 день росту пухлини. Статус метилювання промоторів генів Mmp1 та Mmp8 аналізували за допо-
могою метил-специфічної ПЛР. Рівень метилювання кількісно визначали як співвідношення метильованих
до неметильованих продуктів ПЛР, виражене у відсотках. Результати. У контрольній групі (карцинома Герена
без дексаметазону) промотор Mmp1 був гіпометильований (38—40% метилювання) протягом усього періоду
спостереження. Введення дексаметазону призвело до подальшого незначного зниження метилювання Mmp1
до 32%, хоча й не статистично значущого. Натомість, промотор Mmp8 у пухлинній тканині показав базовий
рівень метилювання 55—57%. Під впливом дексаметазону гіперметилювання Mmp8 спостерігалося вже на
7‑й день (61%) і значно прогресувало до 14-го (67%) та 21-го (69%) дня. Висновок. Наше дослідження де-
монструє, що хронічний стрес, індукований глюкокортикоїдами, змінює епігенетичний профіль пухлинних
клітин, індукуючи диференціальне метилювання генів матриксних металопротеїназ. Зокрема, стрес сприяє
підтримці гіпометилювання MMP1 та значно збільшує гіперметилювання промотора MMP8. Ці результати
свідчать про те, що хронічний стрес може сприяти агресивному фенотипу пухлини через епігенетичну регу-
ляцію ремоделювання позаклітинного матриксу.
Ключові слова: метилювання ДНК, хронічний стрес, рак.
|
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| institution | Experimental Oncology |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-06-15T01:00:26Z |
| publishDate | 2026 |
| publisher | PH Akademperiodyka |
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| spelling | oai:ojs2.ex.aqua-time.com.ua:article-6172026-06-14T20:08:50Z Stress-Induced Changes in the Methylation Status of Mmp1 and Mmp8 Genes in Tumor Tissue of Rats with Guerin Carcinoma СТРЕС-ІНДУКОВАНІ ЗМІНИ СТАТУСУ МЕТИЛЮВАННЯ ГЕНІВ Mmp1 ТА Mmp8 У ПУХЛИННІЙ ТКАНИНІ ЩУРІВ З КАРЦИНОМОЮ ГЕРЕНА Borikun, T. Herasymchuk, Y. метилювання ДНК, хронічний стрес, рак DNA methylation, chronic stress, cancer Background. Chronic stress is a key determinant of public health, signifi &nbsp;antly impacting regulatory systems and potentially contributing to carcinogenesis. Chronic stress, through the activation of the hypothalamic-pituitary- adrenal axis and glucocorticoid signaling, can modify the epigenetic landscape of cells, including DNA meth- ylation. Th s study aimed to evaluate whether chronic glucocorticoid-induced stress modulates the methylation status of the promoter regions of the Mmp1 and Mmp8 genes in the tumor tissue of rats with Guerin carcinoma. Materials and Methods. to simulate chronic stress, dexamethasone (DEX) was administered subcutaneously to laboratory rats with transplanted Guerin carcinoma. tumor samples were collected on days 7, 14, and 21 of tumor growth. The methylation status of the Mmp1 and Mmp8 gene promoters was analyzed using methylation-specifi PCR. The level of methylation was quantifi &nbsp;d as the ratio of methylated to unmethylated PCR products, expressed as a percentage. Results. In the control group (Guerin carcinoma without DEX), the Mmp1 promoter was hypo- methylated (38—40% methylation) throughout the observation period. DEX administration led to a further slight decrease in Mmp1 methylation to 32%, though insignifi &nbsp;ant. In contrast, the Mmp8 promoter in tumor tissue showed baseline methylation levels of 55—57%. Under the influence of DEX, Mmp8 hypermethylation was ob- served as early as day 7 (61%) and signifi &nbsp;antly progressed by day 14 (67%) and day 21 (69%). Conclusion. Our study demonstrated that chronic glucocorticoid-induced stress altered the epigenetic profile of tumor cells by in- ducing differential methylation of the matrix metalloproteinase genes. Specifi &nbsp;ally, it promoted the maintenance of Mmp1 hypomethylation and signifi &nbsp;antly increased the Mmp8 promoter hypermethylation. These fi &nbsp;dings suggest that chronic stress may contribute to an aggressive tumor phenotype through the epigenetic regulation of extracel- lular matrix remodeling. Стан питання. Хронічний стрес є ключовим фактором громадського здоров›я, який суттєво впливає на ре- гуляторні системи та потенційно сприяє канцерогенезу. Хронічний стрес, через активацію гіпоталамо-гіпо- фізарно-надниркової осі та глюкокортикоїдної сигналізації, може змінювати епігенетичний ландшафт клітин, включаючи метилювання ДНК. Метою даного дослідження було оцінити, чи хронічний стрес, викликаний глюкокортикоїдами, модулює метилювання промоторних ділянок генів Mmp1 та Mmp8 у пухлинній тканині щурів з карциномою Герена. Матеріали та методи. Для моделювання хронічного стресу лабораторним щу- рам з трансплантованою карциномою Герена вводили дексаметазон підшкірно. Зразки пухлини збирали на 7, 14 та 21 день росту пухлини. Статус метилювання промоторів генів Mmp1 та Mmp8 аналізували за допо- могою метил-специфічної ПЛР. Рівень метилювання кількісно визначали як співвідношення метильованих до неметильованих продуктів ПЛР, виражене у відсотках. Результати. У контрольній групі (карцинома Герена без дексаметазону) промотор Mmp1 був гіпометильований (38—40% метилювання) протягом усього періоду спостереження. Введення дексаметазону призвело до подальшого незначного зниження метилювання Mmp1 до 32%, хоча й не статистично значущого. Натомість, промотор Mmp8 у пухлинній тканині показав базовий рівень метилювання 55—57%. Під впливом дексаметазону гіперметилювання Mmp8 спостерігалося вже на 7-й день (61%) і значно прогресувало до 14-го (67%) та 21-го (69%) дня. Висновок. Наше дослідження де- монструє, що хронічний стрес, індукований глюкокортикоїдами, змінює епігенетичний профіль пухлинних клітин, індукуючи диференціальне метилювання генів матриксних металопротеїназ. Зокрема, стрес сприяє підтримці гіпометилювання MMP1 та значно збільшує гіперметилювання промотора MMP8. Ці результати свідчать про те, що хронічний стрес може сприяти агресивному фенотипу пухлини через епігенетичну регу- ляцію ремоделювання позаклітинного матриксу. PH Akademperiodyka 2026-06-14 Article Article application/pdf https://exp-oncology.com.ua/index.php/Exp/article/view/617 10.15407/exp-oncology.2026.01.046 Experimental Oncology; Vol. 48 No. 1 (2026): Experimental Oncology; 46-50 Експериментальна онкологія; Том 48 № 1 (2026): Експериментальна онкологія; 46-50 2312-8852 1812-9269 10.15407/exp-oncology.2026.01 en https://exp-oncology.com.ua/index.php/Exp/article/view/617/462 Copyright (c) 2026 Experimental Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| spellingShingle | метилювання ДНК хронічний стрес рак Borikun, T. Herasymchuk, Y. СТРЕС-ІНДУКОВАНІ ЗМІНИ СТАТУСУ МЕТИЛЮВАННЯ ГЕНІВ Mmp1 ТА Mmp8 У ПУХЛИННІЙ ТКАНИНІ ЩУРІВ З КАРЦИНОМОЮ ГЕРЕНА |
| title | СТРЕС-ІНДУКОВАНІ ЗМІНИ СТАТУСУ МЕТИЛЮВАННЯ ГЕНІВ Mmp1 ТА Mmp8 У ПУХЛИННІЙ ТКАНИНІ ЩУРІВ З КАРЦИНОМОЮ ГЕРЕНА |
| title_alt | Stress-Induced Changes in the Methylation Status of Mmp1 and Mmp8 Genes in Tumor Tissue of Rats with Guerin Carcinoma |
| title_full | СТРЕС-ІНДУКОВАНІ ЗМІНИ СТАТУСУ МЕТИЛЮВАННЯ ГЕНІВ Mmp1 ТА Mmp8 У ПУХЛИННІЙ ТКАНИНІ ЩУРІВ З КАРЦИНОМОЮ ГЕРЕНА |
| title_fullStr | СТРЕС-ІНДУКОВАНІ ЗМІНИ СТАТУСУ МЕТИЛЮВАННЯ ГЕНІВ Mmp1 ТА Mmp8 У ПУХЛИННІЙ ТКАНИНІ ЩУРІВ З КАРЦИНОМОЮ ГЕРЕНА |
| title_full_unstemmed | СТРЕС-ІНДУКОВАНІ ЗМІНИ СТАТУСУ МЕТИЛЮВАННЯ ГЕНІВ Mmp1 ТА Mmp8 У ПУХЛИННІЙ ТКАНИНІ ЩУРІВ З КАРЦИНОМОЮ ГЕРЕНА |
| title_short | СТРЕС-ІНДУКОВАНІ ЗМІНИ СТАТУСУ МЕТИЛЮВАННЯ ГЕНІВ Mmp1 ТА Mmp8 У ПУХЛИННІЙ ТКАНИНІ ЩУРІВ З КАРЦИНОМОЮ ГЕРЕНА |
| title_sort | стрес-індуковані зміни статусу метилювання генів mmp1 та mmp8 у пухлинній тканині щурів з карциномою герена |
| topic | метилювання ДНК хронічний стрес рак |
| topic_facet | метилювання ДНК хронічний стрес рак DNA methylation chronic stress cancer |
| url | https://exp-oncology.com.ua/index.php/Exp/article/view/617 |
| work_keys_str_mv | AT borikunt stressinducedchangesinthemethylationstatusofmmp1andmmp8genesintumortissueofratswithguerincarcinoma AT herasymchuky stressinducedchangesinthemethylationstatusofmmp1andmmp8genesintumortissueofratswithguerincarcinoma AT borikunt stresíndukovanízmínistatusumetilûvannâgenívmmp1tammp8upuhlinníjtkaniníŝurívzkarcinomoûgerena AT herasymchuky stresíndukovanízmínistatusumetilûvannâgenívmmp1tammp8upuhlinníjtkaniníŝurívzkarcinomoûgerena |