PPM1M and PRICKLE2 are potential tumor suppressor genes in human clear-cell renal cell carcinoma
Aim. To investigate the expression levels of PPM1M and PRICKLE2 in clear-cell renal cell carcinomas (ccRCC) and propose a mechanism leading to the expression changes in tumor. Methods. Analysis of GEO data, quantitative PCR (Q-PCR), bisulfite sequencing, methylation-specific PCR, deletion search. Re...
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Інститут молекулярної біології і генетики НАН України
2014
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| Цитувати: | PPM1M and PRICKLE2 are potential tumor suppressor genes in human clear-cell renal cell carcinoma / E.E. Rudenko, G.V. Gerashchenko, Y.V. Lapska, S.O. Vozianov, Y.M. Zgonnyk, V.I. Kashuba // Вiopolymers and Cell. — 2014. — Т. 30, № 3. — С. 229-233. — Бібліогр.: 11 назв. — англ. |
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Rudenko, E.E. Gerashchenko, G.V. Lapska, Y.V. Vozianov, S.O. Zgonnyk, Y.M. Kashuba, V.I. 2019-06-15T12:30:58Z 2019-06-15T12:30:58Z 2014 PPM1M and PRICKLE2 are potential tumor suppressor genes in human clear-cell renal cell carcinoma / E.E. Rudenko, G.V. Gerashchenko, Y.V. Lapska, S.O. Vozianov, Y.M. Zgonnyk, V.I. Kashuba // Вiopolymers and Cell. — 2014. — Т. 30, № 3. — С. 229-233. — Бібліогр.: 11 назв. — англ. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.00089A https://nasplib.isofts.kiev.ua/handle/123456789/154299 577.218; 616.006.6 Aim. To investigate the expression levels of PPM1M and PRICKLE2 in clear-cell renal cell carcinomas (ccRCC) and propose a mechanism leading to the expression changes in tumor. Methods. Analysis of GEO data, quantitative PCR (Q-PCR), bisulfite sequencing, methylation-specific PCR, deletion search. Results. We found that the PRICKLE2 expression was down-regulated in 83 % of samples. Decreased expression of PPM1M was shown in 33.3 % of ccRCC samples. The promoters of PPM1M and PRICKLE2 were not methylated, and no deletions were found in their sequences. Conclusions. Our data suggest that PRICKLE2 and PPM1M might be candidates for the tumor suppressor genes in ccRCC. Мета. Дослідити рівень експресії PPM1M і PRICKLE2 у світло- клітинних карциномах нирки (ccRCC) і запропонувати механізм, що призводить до змін експресії генів у пухлинах. Методи. Аналіз баз даних GEO, кількісна ПЛР (Q-ПЛР), бісульфітне секвенування, метил-специфічна ПЛР, пошук делецій. Результати. Ми виявили, що експресія гена PPM1M знижена у 33,3 % зразків ccRCC, у той час як гена PRICKLE2 – у 83 % зразків ccRCC. Метилювання промоторної зони і делеції в генах PPM1M і PRICKLE2 не виявлено. Висновки. Наші дані вказують на те, що PRICKLE2 і PPM1M можуть бути кандидатами в гени-супресори для ccRCC. Цель. Исследовать уровень экспрессии PPM1M и PRICKLE2 в светлоклеточных карциномах почки (ccRCC) и предложить механизм, ведущий к изменениям экспрессии генов в опухолях. Методы. Анализ баз данных GEO, количественная ПЦР (Q-ПЦР), бисульфитное секвенирование, метил-специфическая ПЦР, поиск делеций. Результаты. Мы выявили, что экспрессия гена PPM1M снижена в 33,3 % образцов ccRCC, тогда как гена PRICKLE2 – в 83 % образцов ccRCC. Метилирование промоторной зоны и делеции в генах PPM1M и PRICKLE2 не обнаружены. Выводы. Наши данные показывают, что PRICKLE2 и PPM1M могут быть кандидатами в гены-супрессоры для ccRCC. en Інститут молекулярної біології і генетики НАН України Вiopolymers and Cell Biomedicine PPM1M and PRICKLE2 are potential tumor suppressor genes in human clear-cell renal cell carcinoma PPM1M і PRICKLE2 як потенційні гени – супресори пухлин у світлоклітинній карциномі нирки людини PPM1M и PRICKLE2 как потенциальные гены – супрессоры опухолей в светлоклеточной карциноме почки человека Article published earlier |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| title |
PPM1M and PRICKLE2 are potential tumor suppressor genes in human clear-cell renal cell carcinoma |
| spellingShingle |
PPM1M and PRICKLE2 are potential tumor suppressor genes in human clear-cell renal cell carcinoma Rudenko, E.E. Gerashchenko, G.V. Lapska, Y.V. Vozianov, S.O. Zgonnyk, Y.M. Kashuba, V.I. Biomedicine |
| title_short |
PPM1M and PRICKLE2 are potential tumor suppressor genes in human clear-cell renal cell carcinoma |
| title_full |
PPM1M and PRICKLE2 are potential tumor suppressor genes in human clear-cell renal cell carcinoma |
| title_fullStr |
PPM1M and PRICKLE2 are potential tumor suppressor genes in human clear-cell renal cell carcinoma |
| title_full_unstemmed |
PPM1M and PRICKLE2 are potential tumor suppressor genes in human clear-cell renal cell carcinoma |
| title_sort |
ppm1m and prickle2 are potential tumor suppressor genes in human clear-cell renal cell carcinoma |
| author |
Rudenko, E.E. Gerashchenko, G.V. Lapska, Y.V. Vozianov, S.O. Zgonnyk, Y.M. Kashuba, V.I. |
| author_facet |
Rudenko, E.E. Gerashchenko, G.V. Lapska, Y.V. Vozianov, S.O. Zgonnyk, Y.M. Kashuba, V.I. |
| topic |
Biomedicine |
| topic_facet |
Biomedicine |
| publishDate |
2014 |
| language |
English |
| container_title |
Вiopolymers and Cell |
| publisher |
Інститут молекулярної біології і генетики НАН України |
| format |
Article |
| title_alt |
PPM1M і PRICKLE2 як потенційні гени – супресори пухлин у світлоклітинній карциномі нирки людини PPM1M и PRICKLE2 как потенциальные гены – супрессоры опухолей в светлоклеточной карциноме почки человека |
| description |
Aim. To investigate the expression levels of PPM1M and PRICKLE2 in clear-cell renal cell carcinomas (ccRCC) and propose a mechanism leading to the expression changes in tumor. Methods. Analysis of GEO data, quantitative PCR (Q-PCR), bisulfite sequencing, methylation-specific PCR, deletion search. Results. We found that the PRICKLE2 expression was down-regulated in 83 % of samples. Decreased expression of PPM1M was shown in 33.3 % of ccRCC samples. The promoters of PPM1M and PRICKLE2 were not methylated, and no deletions were found in their sequences. Conclusions. Our data suggest that PRICKLE2 and PPM1M might be candidates for the tumor suppressor genes in ccRCC.
Мета. Дослідити рівень експресії PPM1M і PRICKLE2 у світло- клітинних карциномах нирки (ccRCC) і запропонувати механізм, що призводить до змін експресії генів у пухлинах. Методи. Аналіз баз даних GEO, кількісна ПЛР (Q-ПЛР), бісульфітне секвенування, метил-специфічна ПЛР, пошук делецій. Результати. Ми виявили, що експресія гена PPM1M знижена у 33,3 % зразків ccRCC, у той час як гена PRICKLE2 – у 83 % зразків ccRCC. Метилювання промоторної зони і делеції в генах PPM1M і PRICKLE2 не виявлено. Висновки. Наші дані вказують на те, що PRICKLE2 і PPM1M можуть бути кандидатами в гени-супресори для ccRCC.
Цель. Исследовать уровень экспрессии PPM1M и PRICKLE2 в светлоклеточных карциномах почки (ccRCC) и предложить механизм, ведущий к изменениям экспрессии генов в опухолях. Методы. Анализ баз данных GEO, количественная ПЦР (Q-ПЦР), бисульфитное секвенирование, метил-специфическая ПЦР, поиск делеций. Результаты. Мы выявили, что экспрессия гена PPM1M снижена в 33,3 % образцов ccRCC, тогда как гена PRICKLE2 – в 83 % образцов ccRCC. Метилирование промоторной зоны и делеции в генах PPM1M и PRICKLE2 не обнаружены. Выводы. Наши данные показывают, что PRICKLE2 и PPM1M могут быть кандидатами в гены-супрессоры для ccRCC.
|
| issn |
0233-7657 |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/154299 |
| citation_txt |
PPM1M and PRICKLE2 are potential tumor suppressor genes in human clear-cell renal cell carcinoma / E.E. Rudenko, G.V. Gerashchenko, Y.V. Lapska, S.O. Vozianov, Y.M. Zgonnyk, V.I. Kashuba // Вiopolymers and Cell. — 2014. — Т. 30, № 3. — С. 229-233. — Бібліогр.: 11 назв. — англ. |
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| fulltext |
BIOMEDICINE
UDC 577.218; 616.006.6
PPM1M and PRICKLE2 are potential tumor suppressor
genes in human clear-cell renal cell carcinoma
E. E. Rudenko1, G. V. Gerashchenko1, Y. V. Lapska1, S. O. Vozianov2,
Y. M. Zgonnyk2, V. I. Kashuba1
1Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143
2Institute of Urology, NAMS of Ukraine
9A, Kotsubinskoho Str., Kyiv, Ukraine, 04053
rudenko_jene@ukr.net
Aim. To investigate the expression levels of PPM1M and PRICKLE2 in clear-cell renal cell carcinomas
(ccRCC) and propose a mechanism leading to the expression changes in tumor. Methods. Analysis of GEO data,
quantitative PCR (Q-PCR), bisulfite sequencing, methylation-specific PCR, deletion search. Results. We found
that the PRICKLE2 expression was down-regulated in 83 % of samples. Decreased expression of PPM1M was
shown in 33.3 % of ccRCC samples. The promoters of PPM1M and PRICKLE2 were not methylated, and no de-
letions were found in their sequences. Conclusions. Our data suggest that PRICKLE2 and PPM1M might be
candidates for the tumor suppressor genes in ccRCC.
Keywords: renal cell carcinoma, genetic and epigenetic regulation, quantitative real time PCR, deletion, me-
thylation status.
Introduction. Kidney cancer is a malignant tumor main-
ly of epithelial origin and is derived from the cells of pro-
ximal convoluted tubule. Clear-cell renal cell carcino-
ma (ccRCC) accounts 70–80 % of all renal cancer cases
and is characterized by chemo- and radio-resistance
[1]. According to the NotI-microarrays, the PPM1M
and PRICKLE2 genes showed the presence of methy-
lation/deletion more than in 20 % of ccRCC tumor
samples [2]. We performed an analysis of the GEO data
base for the PPM1M and PRICKLE2 genes (http://www.
ncbi.nlm.nih.gov/geoprofiles/) and investigated their
expression in ccRCC. An exact physiological role and
function of PPM1M and PRICKLE2 in human’s car-
cinogenesis is not known for now. It is known, how-
ever, that encoded proteins are the members of cancer-
related pathways. PPM1M inhibits the IL-1-NF-kap-
paB signaling pathway by selective dephosphorylation
of IKKbeta [3]. PRICKLE2 is involved in the WNT/
planar cell polarity (PCP) signaling pathway that cont-
rols tissue polarity and cell movement [4]. These genes
are tumor suppressor candidates in cervical cancer,
non-small cell lung cancer and ovarian cancer [5–7]. It
is possible, that these two genes might be potential tu-
mor-suppressor genes in ccRCC as well. The present pa-
per is devoted to a detailed study on the PPM1M and
PRICKLE2 gene expression in ccRCC.
Materials and methods. Tissue samples. Surgical-
ly removed tumors and surrounding rim of normal tis-
sue were obtained from Kyiv National Urological Cen-
ter (Ukraine). All tumor specimens were assessed accor-
ding to the WHO International System of Clinico-Mor-
phological Classification of Tumors (TNM). All samp-
les were obtained according to the guidelines of the Ethi-
cal Committee of IMBG.
Isolation of DNA and total RNA. DNA samples we-
re isolated, using GeneJET Genomic DNA Purification
229
ISSN 0233–7657. Biopolymers and Cell. 2014. Vol. 30. N 3. P. 229–233 doi: http://dx.doi.org/10.7124/bc.00089A
� Institute of Molecular Biology and Genetics, NAS of Ukraine, 2014
Kit («Fermentas», Lithuania). Total RNA was isolated,
using RNeasy Mini Kit («QIAGEN», USA). cDNA
was synthesized, using RevertAid First Strand cDNA
Synthesis Kits («Fermentas»). All procedures were per-
formed according to the manufacturer’s recommen-
dations.
Analysis of gene expression levels. The analysis of
relative expression of PPM1M and PRICKLE2 genes
was performed with the help of Q-PCR, using Master
mix SYBR Green («Fermentas») and IQ5 Cycler («Bio
Rad», USA) [8]. The primers were designed, using the
Primer3 (http://frodo.wi.mit.edu/primer3/) and IDT
(http://eu.idtdna.com/site) programs (Table 1). TBP was
used as a reference gene [9].
Methylation status analysis. The analysis of methy-
lation status of the PPM1M and PRICKLE2 promoter
regions was performed by methyl specific PCR as was
described previously [10].
Deletion search for the PPM1M and PRICKLE2
genes was performed, using PCR with primers for de-
letion search from NCBI database (Table 1) and sub-
sequent analysis of products length in denaturing
PAAG electrophoresis. PCR was performed under the
standard conditions [10].
Statistical analysis was performed as described
previously [8].
Results and discussions. In the current study 19
samples of ccRCC at the stage 1–4 and corresponding
«normal» tissues were analyzed. The mean age of
patients was 56 ± 3.75 (in the range of 46–69 years),
with a male-to-female ratio of 58 % and 42 % respec-
tively (Table 2). The samples were grouped according
to the stage of tumor development and arranged in
order of increasing atypia (Fig. 1, 2, Table 2).
The relative PPM1M gene expression analysis by
Q-PCR allowed us to separate the tumor samples into
three groups – with low, unchanged, and a high gene ex-
pression. The increased PPM1M expression was detec-
ted in 50 % of the samples (9 of 18). The expression of
PPM1M was decreased in 33.3 % (6 out of 18) samples.
In 16.7 % of cases (3 out of 18) statistically significant
changes were not found.
PRICKLE2 was downregulated in the majority of
samples (83 %, 15 out of 18). No correlation between
age, sex, or stage of atypia was observed for both
studied genes. (Fig. 2, Table 2).
In order to explain the gene expression changes,
promoter methylation was investigated, using MSP
PCR. No correlation between the gene expression level
and PPM1M promoter methylation status was found.
Moreover, there were no CpG islands in the promoter
area of the PRICKLE2 gene.
To study the putative deletions as one of the reasons
of expression changes, we chose two pairs of primers
(D3S1287, D3S4182) for PRICKLE2 using NCBI da-
tabase. No homozygous deletions were identified. Four
pairs of primers for the PPM1M gene (A002C09,
MARC_15661, RH76369, RH12810) were also selec-
ted (Table 1). No homozygous deletions were identifi-
ed. Further, primers for sequence that contained CA re-
peats were selected independently. All samples were
homozygous for the indicated loci; that means that a stu-
dy on heterozygous deletions was not possible. No ho-
mozygous deletions were identified.
As a result of our work no deletions or promoter me-
thylation of PPM1M and PRICKLE2 were found. This
corresponds to a low percentage of methylation/deletion
changes in the microarray analysis of these genes [2].
The PRICKLE2 gene encodes the prickle-like 2 pro-
tein that is one of the essential proteins in the Wnt-path-
way, determining planar cell polarity (PCP). Thee prick-
le-like protein 2 participates also in the remodeling of
cytoskeleton, change of cellular adhesion and mobility
[11]. In this study we showed down-regulation of
PRICKLE2. This may be associated with dedifferentia-
tion processes and loss of the typical morphology of
cells in the malignant transformation.
The PPM1M gene encodes a protein with phospha-
tase activity. A function of this protein was studied on-
ly in mice. However, it is known, that Ððm1m partici-
pates in the IL1-induction pathway by NF-�B. The
Ððm1m dephosphorylates I�B that blocks activation of
NF-�B, preventing the induction of inflammation-
related proteins [3]. Therefore, the highly expressed
PPM1M gene might be involved in the formation of ac-
tive inflammatory lesion that surrounds neoplasm. Our
data show that the PPM1M expression in ccRCC can
be reduced as well as increased or remain unchanged,
that might indicate a variety of ways to block NF-�B in
tumors.
The absence of correlation between the expression
decrease and methylation or deletions suggests that the
230
RUDENKO E. E. ET AL.
231
PPM1M AND PRICKLE2 ARE POTENTIAL TUMOR SUPPRESSOR GENES IN RENAL CARCINOMA
Primer’s title
(name)
Primer’s sequence
Primer’s title
(name)
Primer’s sequence
PPM1M
(expression)
for 5'-GATGTACTGTCCAACGAGCAG-3'
rev 5'-TGTCTTCCTTTCCCTGTGTG-3' MARC_1566
1
for 5'-CTGGGAACACTGGCTGTCTC-3'
rev 5'-GTAGGACACCTGCCCTTCCT-3'
PRICKLE2
(expression)
for 5'- TGCCCTATTGAGGAGAAGGA-3'
rev 5'-TAATGGTTGTGATGGAGGAAT-3'
RH76369
for 5'-TTGAGATGGATGTGTGTTGAGG-3'
rev 5'-GAAGGGCAGGTGTCCTACG-3'
TBP
(expression)
for 5'-GAACCACGGCACTGATTTTC-3'
rev 5'-CACAGCTCCCCACCATATTC-3'
RH12810
for 5'-GTTGGGGCATCAGACCAG-3'rev
5'-GGGTAGAGCACAAGGGACAA-3'
D3S1287
for 5'-ATAACACAACAAGCAAGCCTATGGT-3'
rev 5'-GAGTGACATTTGCCCCTTTG-3'
PPM1M-CA
for 5'-CAGCACCTTATCCCCA-3'
rev 5'-TGGGATGACTTGCTGTGT-3'
D3S4182
for 5'-AAGTGTTCAGAACAGTCTCTGGC-3'
rev 5'-AACAAAACCTCAAAGGGCCT-3'
PPM1M-MS
P Met
for 5'-CGT GTT TTA TCG ACG GTT TC-3'rev
5'-AAC GTA CGT CCT CGT ACG AA-3'
A002C09
for 5'-GTTAAGAGGCAGGCTACTAC-3'
rev 5'-CTGAAAAGAGACCAGTTC-3'
PPM1M-MS
P Unmet
for 5'-AGT TTTGTGTTTTATTGATGGTTTT-3'
rev 5'-CCAAAATAACATACATCCTCATACA-3'
Table 1
Primers for target and reference genes to study expression levels, deletion search and methylation analysis
Sample N Sex Stage of atypia Age TNM classification PPM1M, RE PRICKLE2, RE
1 F 1 49 T2N0M0 0,367 ± 0,062 No signal
2 M 1 57 T2N0M0 3,11 ± 0,437 0,549 ± 0,001
3 M 1 49 T2N0M1 2,353 ± 0,012 0,442 ± 0,017
4 M 1 57 T2N0M0 0,177 ± 0,014 2,667 ± 0,045
5 F 1 57 T2N0M0 4,116 ± 0,272 0,632 ± 0,033
6 F 1 73 T2N0M0 0,521 ± 0,003 1,613 ± 0,090
7 M 1 61 T2N0M0 0,991 ± 0,031 0,340 ± 0,035
8 M 1 50 T2N0M0 1,747 ± 0,009 0,514 ± 0,031
9 F 1 57 T2N0M0 1,062 ± 0,033 0,453 ± 0,080
10 F 2 69 T2N0M0 6,299 ± 0,078 0,102 ± 0,002
11 F 2 50 T2N0M0 0,279 ± 0,121 0,213 ± 0,007
12 M 2 55 T2N0M0 0,048 ± 0,010 0,118 ± 0,052
13 F 2 66 T2N0M0 0,919 ± 0,114 1,882 ± 0,484
14 M 2 49 T2N0M0 2,028 ± 0,020 0,141 ± 0,003
15 M 2 49 T2N0M0 No signal 0,630 ± 0,094
16 M 3 46 T3N0M0 1,86 ± 0,265 0,508 ± 0,020
17 M 4 51 T2N1M1 1,318 ± 0,147 0,618 ± 0,014
18 M 4 58 T3N0M0 4,173 ± 0,605 0,205 ± 0,014
19 F 4 61 T3N0M0 0,715 ± 0,073 0,025 ± 0,005
Table 2
Clinical characteristics and relative expression level (RE) of PPM1M and PRICKLE2 genes in ccRCC patients
changes in PPM1M and PRICKLE2 gene expression in
ccRCC might be achieved by other mechanisms. It is
possible that miRNAs or other proteins might be invol-
ved in regulation of mRNA expression.
Conclusions. For the first time the PPM1M and
PRICKLE2 genes expression has been analyzed in
ccRCC by the Q-PCR method. In the present work, we
have found, that the PPM1M expression is increased in
50 % of the samples. The expression of PRICKLE2 was
downregulated in 83 % of samples. Neither deletions
nor methylation were a reason for a decline of the
PPM1M and PRICKLE2 expression. This indicates that
another mechanism, that is not associated with DNA,
aberrations is involved in the expression changes. Ta-
king into consideration the functions of proteins, that
are encoded by the PPM1M and PRICKLE2 genes, we
can suggest their involvement in the kidney carcinoge-
nesis. Based on obtained results, the PRICKLE2 gene
might be a candidate for a tumor suppressor gene. Fur-
ther studies are required to explain the mechanisms of
detected changes in the PPM1M and PRICKLE2 e-
xpression.
Funding. This work was partially supported by the
project «Identification of molecular genetic markers
for diagnostics of malignant neoplasms of epithelial
origin», state registration N 0110U004744.
PPM1M ³ PRICKLE2 ÿê ïîòåíö³éí³ ãåíè – ñóïðåñîðè ïóõëèí ó
ñâ³òëîêë³òèíí³é êàðöèíîì³ íèðêè ëþäèíè
ª. ª. Ðóäåíêî, Ã. Â. Ãåðàùåíêî, Þ. Â. Ëàïñüêà, Ñ. Î. Âîç³àíîâ,
Þ. Ì. Çãîííèê, Â. ². Êàøóáà
Ðåçþìå
Ìåòà. Äîñë³äèòè ð³âåíü åêñïðåñ³¿ PPM1M ³ PRICKLE2 ó ñâ³òëî-
êë³òèííèõ êàðöèíîìàõ íèðêè (ccRCC) ³ çàïðîïîíóâàòè ìåõàí³çì,
ùî ïðèçâîäèòü äî çì³í åêñïðåñ³¿ ãåí³â ó ïóõëèíàõ. Ìåòîäè. Àíàë³ç
áàç äàíèõ GEO, ê³ëüê³ñíà ÏËÐ (Q-ÏËÐ), á³ñóëüô³òíå ñåêâåíóâàí-
íÿ, ìåòèë-ñïåöèô³÷íà ÏËÐ, ïîøóê äåëåö³é. Ðåçóëüòàòè. Ìè âèÿâè-
ëè, ùî åêñïðåñ³ÿ ãåíà PPM1M çíèæåíà ó 33,3 % çðàçê³â ccRCC, ó
òîé ÷àñ ÿê ãåíà PRICKLE2 – ó 83 % çðàçê³â ccRCC. Ìåòèëþâàííÿ
232
RUDENKO E. E. ET AL.
0.01
0.1
1
10
1 2 3 4 5 6 7 8 9 10 11 12 13 14 16 17 18 19
Sample number up to increase stage of atypia
P
P
M
1
M
ex
p
re
ss
io
n
le
v
el
,
lg
(R
)
Fig. 1. Relative expression of
PPM1M (n = 18) in ccRCC. Samp-
les 1–14 – stage 1–2; 16–19 – sta-
ge 3–4
0.01
0.1
1
10
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Sample number up to increase stage of atypia
P
R
IC
K
L
E
ex
p
re
ss
io
n
le
v
el
,
lg
(R
)
Fig. 2. Relative expression of
PRICKLE2 (n = 18) in ccRCC.
Samples 2–14 – stage 1–2; 15–
19 – stage 3–4
ïðîìîòîðíî¿ çîíè ³ äåëåö³¿ â ãåíàõ PPM1M ³ PRICKLE2 íå âèÿâëå-
íî. Âèñíîâêè. Íàø³ äàí³ âêàçóþòü íà òå, ùî PRICKLE2 ³ PPM1M
ìîæóòü áóòè êàíäèäàòàìè â ãåíè-ñóïðåñîðè äëÿ ccRCC.
Êëþ÷îâ³ ñëîâà: ñâ³òëîêë³òèííà êàðöèíîìà íèðêè, ãåíåòè÷íà ³
åï³ãåíåòè÷íà ðåãóëÿö³ÿ, ê³ëüê³ñíà ÏËÐ ó ðåàëüíîìó ÷àñ³, äåëåö³¿,
ñòàòóñ ìåòèëþâàííÿ.
PPM1M è PRICKLE2 êàê ïîòåíöèàëüíûå ãåíû – ñóïðåññîðû
îïóõîëåé â ñâåòëîêëåòî÷íîé êàðöèíîìå ïî÷êè ÷åëîâåêà
Å. Å. Ðóäåíêî, À. Â. Ãåðàùåíêî, Þ. Â. Ëàïñêàÿ, Ñ. À. Âîçèàíîâ,
Þ. Ì. Çãîííèê, Â. È. Êàøóáà
Ðåçþìå
Öåëü. Èññëåäîâàòü óðîâåíü ýêñïðåññèè PPM1M è PRICKLE2 â
ñâåòëîêëåòî÷íûõ êàðöèíîìàõ ïî÷êè (ccRCC) è ïðåäëîæèòü ìåõà-
íèçì, âåäóùèé ê èçìåíåíèÿì ýêñïðåññèè ãåíîâ â îïóõîëÿõ. Ìåòîäû.
Àíàëèç áàç äàííûõ GEO, êîëè÷åñòâåííàÿ ÏÖÐ (Q-ÏÖÐ), áèñóëü-
ôèòíîå ñåêâåíèðîâàíèå, ìåòèë-ñïåöèôè÷åñêàÿ ÏÖÐ, ïîèñê äåëå-
öèé. Ðåçóëüòàòû. Ìû âûÿâèëè, ÷òî ýêñïðåññèÿ ãåíà PPM1M ñíè-
æåíà â 33,3 % îáðàçöîâ ccRCC, òîãäà êàê ãåíà PRICKLE2 – â 83 %
îáðàçöîâ ccRCC. Ìåòèëèðîâàíèå ïðîìîòîðíîé çîíû è äåëåöèè â
ãåíàõ PPM1M è PRICKLE2 íå îáíàðóæåíû. Âûâîäû. Íàøè äàí-
íûå ïîêàçûâàþò, ÷òî PRICKLE2 è PPM1M ìîãóò áûòü êàíäèäà-
òàìè â ãåíû-ñóïðåññîðû äëÿ ccRCC.
Êëþ÷åâûå ñëîâà: ñâåòëîêëåòî÷íàÿ êàðöèíîìà ïî÷åê, ãåíåòè-
÷åñêàÿ è ýïèãåíåòè÷åñêàÿ ðåãóëÿöèÿ, êîëè÷åñòâåííàÿ ÏÖÐ â ðåàëü-
íîì âðåìåíè, äåëåöèè, ñòàòóñ ìåòèëèðîâàíèÿ.
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Received 25.02.14
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