Epigenetic regulation of APC in the molecular pathogenesis of gallbladder cancer
Background & objectives: Loss of function of adenomatous polyposis coli (APC) has been reported in cancer. The two promoters of APC, 1A and 1B also have roles in cancer. But, the epigenetic role of APC promoters is not yet clear in gallbladder cancer (GBC) and gallstone diseases (GSD). We undert...
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doaj-091835f05d75493593746e03040038dd2020-11-24T23:46:58ZengWolters Kluwer Medknow PublicationsIndian Journal of Medical Research0971-59162016-01-011437829010.4103/0971-5916.191792Epigenetic regulation of APC in the molecular pathogenesis of gallbladder cancerDinesh Singh TekchamSatish S PoojaryShushruta BhuniaMustafa Ahmed BarbhuiyaSanjeev GuptaBraj Raj ShrivastavPramod Kumar TiwariBackground & objectives: Loss of function of adenomatous polyposis coli (APC) has been reported in cancer. The two promoters of APC, 1A and 1B also have roles in cancer. But, the epigenetic role of APC promoters is not yet clear in gallbladder cancer (GBC) and gallstone diseases (GSD). We undertook this study to determine the epigenetic role of APC in GBC and GSD. Methods: Methylation-specific (MS)-PCR was used to analyze the methylation of APC gene. The expression of APC gene was studied by semi-quantitative PCR, real-time PCR and immunohistochemistry (IHC) in GBC, GSD and adjacent normal tissues. Results: Of the two promoters, APC 1A promoter was found methylated in 96 per cent GBC ( P=0.0155) and 80 per cent GSD (P=0.015). Exon 1 was downregulated in grade II (P=0.002) and grade III (P=0.0001) of GBC, while exon 2 was normally expressed. Scoring analysis of IHC revealed 0 or negativity in 34.48 per cent (P=0.057) and 1+ in 24.14 per cent (P=0.005) GBC cases suggesting loss of APC expression. Interpretation & conclusions: The present findings indicate epigenetic silencing of APC in advanced GBC. The methylation pattern, followed by expression analysis of APC may be suggested for diagnostic, prognostic and therapeutic purposes in GBC in future.http://www.ijmr.org.in/article.asp?issn=0971-5916;year=2016;volume=143;issue=7;spage=82;epage=90;aulast=TekchamAdenomatous polyposis coli - epigenetics - gallbladder cancer - gallstone disease - tissue microarray |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dinesh Singh Tekcham Satish S Poojary Shushruta Bhunia Mustafa Ahmed Barbhuiya Sanjeev Gupta Braj Raj Shrivastav Pramod Kumar Tiwari |
spellingShingle |
Dinesh Singh Tekcham Satish S Poojary Shushruta Bhunia Mustafa Ahmed Barbhuiya Sanjeev Gupta Braj Raj Shrivastav Pramod Kumar Tiwari Epigenetic regulation of APC in the molecular pathogenesis of gallbladder cancer Indian Journal of Medical Research Adenomatous polyposis coli - epigenetics - gallbladder cancer - gallstone disease - tissue microarray |
author_facet |
Dinesh Singh Tekcham Satish S Poojary Shushruta Bhunia Mustafa Ahmed Barbhuiya Sanjeev Gupta Braj Raj Shrivastav Pramod Kumar Tiwari |
author_sort |
Dinesh Singh Tekcham |
title |
Epigenetic regulation of APC in the molecular pathogenesis of gallbladder cancer |
title_short |
Epigenetic regulation of APC in the molecular pathogenesis of gallbladder cancer |
title_full |
Epigenetic regulation of APC in the molecular pathogenesis of gallbladder cancer |
title_fullStr |
Epigenetic regulation of APC in the molecular pathogenesis of gallbladder cancer |
title_full_unstemmed |
Epigenetic regulation of APC in the molecular pathogenesis of gallbladder cancer |
title_sort |
epigenetic regulation of apc in the molecular pathogenesis of gallbladder cancer |
publisher |
Wolters Kluwer Medknow Publications |
series |
Indian Journal of Medical Research |
issn |
0971-5916 |
publishDate |
2016-01-01 |
description |
Background & objectives: Loss of function of adenomatous polyposis coli (APC) has been reported in cancer. The two promoters of APC, 1A and 1B also have roles in cancer. But, the epigenetic role of APC promoters is not yet clear in gallbladder cancer (GBC) and gallstone diseases (GSD). We undertook this study to determine the epigenetic role of APC in GBC and GSD.
Methods: Methylation-specific (MS)-PCR was used to analyze the methylation of APC gene. The expression of APC gene was studied by semi-quantitative PCR, real-time PCR and immunohistochemistry (IHC) in GBC, GSD and adjacent normal tissues.
Results: Of the two promoters, APC 1A promoter was found methylated in 96 per cent GBC ( P=0.0155) and 80 per cent GSD (P=0.015). Exon 1 was downregulated in grade II (P=0.002) and grade III (P=0.0001) of GBC, while exon 2 was normally expressed. Scoring analysis of IHC revealed 0 or negativity in 34.48 per cent (P=0.057) and 1+ in 24.14 per cent (P=0.005) GBC cases suggesting loss of APC expression.
Interpretation & conclusions: The present findings indicate epigenetic silencing of APC in advanced GBC. The methylation pattern, followed by expression analysis of APC may be suggested for diagnostic, prognostic and therapeutic purposes in GBC in future. |
topic |
Adenomatous polyposis coli - epigenetics - gallbladder cancer - gallstone disease - tissue microarray |
url |
http://www.ijmr.org.in/article.asp?issn=0971-5916;year=2016;volume=143;issue=7;spage=82;epage=90;aulast=Tekcham |
work_keys_str_mv |
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