کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2515098 1118500 2006 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Epigenetic control of CTCFL/BORIS and OCT4 expression in urogenital malignancies
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Epigenetic control of CTCFL/BORIS and OCT4 expression in urogenital malignancies
چکیده انگلیسی

Aberrant hypomethylation in many cancers reactivates retrotransposons and selected single-copy genes such as cancer-testis antigens. Genes reactivated in this manner have recently been postulated to include CTCFL/BORIS, a presumptive testis-specific chromatin regulator, and OCT4/POU5F1, a transcriptional activator in pluripotent cells. We found both genes expressed at high levels in testis and at much lower levels in normal prostate tissue. In prostate and bladder carcinoma cell lines and cancer tissues expression remained largely unchanged, but individual prostate carcinomas showed modestly increased CTCFL expression compared to normal tissues. OCT4 expression was significantly decreased in cancer tissues. Promoter methylation in both genes paralleled expression levels. CTCFL, but not OCT4 was dramatically induced in cancer cell lines by 5-aza-2′-deoxycytidine, but neither gene by the histone deacetylase inhibitor suberoylanilide hydroxamic acid. Thus, CTCFL and OCT4 resemble cancer-testis antigens in being selectively hypomethylated and expressed in male germ cells but differ in lacking significant reexpression and hypomethylation in prostate carcinomas. DNA methylation appears the crucial mechanism in the control of CTCFL transcription, but less decisive in that of OCT4. These findings imply that inhibitors of DNA methylation used for cancer treatment may induce CTCFL expression. Immunohistochemistry demonstrated nuclear localization of CTCFL in developing spermatocytes, and cytoplasmatic localization in spermatogonia, Leydig cells, and epithelial prostate cells. Teratocarcinoma cell lines showed nuclear, and 5-aza-2′-deoxycytidine-treated prostate cancer lines nuclear or cytoplasmatic localization. These different localizations might indicate additional control of CTCFL function via intracellular compartmentation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 72, Issue 11, 30 November 2006, Pages 1577–1588
نویسندگان
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