Academic Journal
Functional role and tobacco smoking effects on methylation ofCYP1A1gene in prostate cancer
| Title: | Functional role and tobacco smoking effects on methylation ofCYP1A1gene in prostate cancer |
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| Authors: | Mitsui, Yozo, Chang, Inik, Kato, Taku, Hashimoto, Yutaka, Yamamura, Soichiro, Fukuhara, Shinichiro, Wong, Darryn K, Shiina, Marisa, Imai-Sumida, Mitsuho, Majid, Shahana, Saini, Sharanjot, Shiina, Hiroaki, Nakajima, Koichi, Deng, Guoren, Dahiya, Rajvir, Tanaka, Yuichiro |
| Contributors: | College of Dentistry, Dept. of Oral Biology, Yozo Mitsui, Inik Chang, Taku Kato, Yutaka Hashimoto, Soichiro Yamamura, Shinichiro Fukuhara, Darryn K. Wong, Marisa Shiina, Mitsuho Imai-Sumida, Shahana Majid, Sharanjot Saini, Hiroaki Shiina, Koichi Nakajima, Guoren Deng, Rajvir Dahiya, Yuichiro Tanaka, Chang, In Ik |
| Source: | Oncotarget Oncotarget, vol 7, iss 31 |
| Publisher Information: | Impact Journals, LLC, 2016. |
| Publication Year: | 2016 |
| Subject Terms: | Male, Aging, Prostatic Hyperplasia, Apoptosis, Polymerase Chain Reaction, Epigenesis, Genetic, 80 and over, 2.1 Biological and endogenous factors, Azacitidine/analogs & derivatives, Aetiology, Prostatic Neoplasms/metabolism, Promoter Regions, Genetic, Cancer, Oligonucleotide Array Sequence Analysis, Aged, 80 and over, DNA Methylation, Azacitidine/chemistry, Tumor, Prostatic Neoplasms/genetics, Prostate Cancer, Middle Aged, prostate cancer, 3. Good health, Gene Expression Regulation, Neoplastic, Enhancer Elements, Genetic, Azacitidine, Cytochrome P-450 CYP1A1/metabolism, cytochrome P450 1A1, Biotechnology, Research Paper, Urologic Diseases, Enhancer Elements, Oncology and Carcinogenesis, Decitabine, Cell Line, Xenobiotics, Promoter Regions, Genetic, Cell Line, Tumor, Tobacco, Genetics, Tobacco Smoking, Cytochrome P-450 CYP1A1, Sulfites, Humans, tobacco smoking, Aged, Neoplastic, Tobacco Smoke and Health, Cytochrome P-450 CYP1A1/genetics, Prevention, Gene Expression Profiling, Prostatic Hyperplasia/metabolism, Prostatic Neoplasms, Prostatic Hyperplasia/genetics, Gene Expression Regulation, Tissue Array Analysis, Tobacco Smoking/adverse effects, CpG Islands, methylation, Sulfites/chemistry, Xenobiotics/chemistry, Epigenesis |
| Description: | Cytochrome P450 (CYP) 1A1 is a phase I enzyme that can activate various compounds into reactive forms and thus, may contribute to carcinogenesis. In this study, we investigated the expression, methylation status, and functional role of CYP1A1 on prostate cancer cells. Increased expression of CYP1A1 was observed in all cancer lines (PC-3, LNCaP, and DU145) compared to BPH-1 (P < 0.05); and was enhanced further by 5-aza-2'-deoxycytidine treatment (P < 0.01). Methylation-specific PCR (MSP) and sequencing of bisulfite-modified DNA of the xenobiotic response element (XRE) enhancer site XRE-1383 indicated promoter methylation as a regulator of CYP1A1 expression. In tissue, microarrays showed higher immunostaining of CYP1A1 in prostate cancer than normal and benign prostatic hyperplasia (BPH; P < 0.001), and methylation analyses in clinical specimens revealed significantly lower methylation levels in cancer compared to BPH at all enhancer sites analyzed (XRE-1383, XRE-983, XRE-895; P < 0.01). Interestingly, smoking affected the XRE-1383 site where the methylation level was much lower in cancer tissues from smokers than non-smokers (P < 0.05). CYP1A1 levels are thus increased in prostate cancer and to determine the functional effect of CYP1A1 on cells, we depleted the gene in LNCaP and DU145 by siRNA. We observe that CYP1A1 knockdown decreased cell proliferation (P < 0.05) and increased apoptosis (P < 0.01) in both cell lines. We analyzed genes affected by CYP1A1 silencing and found that apoptosis-related BCL2 was significantly down-regulated. This study supports an oncogenic role for CYP1A1 in prostate cancer via promoter hypomethylation that is influenced by tobacco smoking, indicating CYP1A1 to be a promising target for prostate cancer treatment. |
| Document Type: | Article Other literature type |
| File Description: | application/pdf |
| Language: | English |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.9470 |
| Access URL: | http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=9470&path%5B%5D=29437 https://pubmed.ncbi.nlm.nih.gov/27203547 https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201902205667856850 https://escholarship.org/content/qt22s2h59f/qt22s2h59f.pdf?t=qanpgh https://www.oncotarget.com/fulltext/9470 https://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=9470 http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=9470&path%5B%5D=0 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226494/ https://escholarship.org/uc/item/22s2h59f https://escholarship.org/content/qt22s2h59f/qt22s2h59f.pdf |
| Rights: | CC BY CC BY NC ND |
| Accession Number: | edsair.doi.dedup.....cf5c5f3f4c15173f1324622c71d608c4 |
| Database: | OpenAIRE |
| ISSN: | 19492553 |
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| DOI: | 10.18632/oncotarget.9470 |