BORIS in human cancers -- a review.
Brother of the regulator of the imprinted site (BORIS) or CTCFL is an 11 zinc finger (ZF) protein, which is considered to be a new oncogene. It is a paralogue of CCCTC-binding factor (CTCF), generated by a duplication event. BORIS is highly expressed in primary spermatocytes, although it is silenced at later stages of spermatogenesis. BORIS has either not been found in normal human tissues or cells or has been detected at very low levels. The expression of the BORIS gene is predominantly controlled by DNA-methylation, while its activation requires the demethylation of its promoter. Re-expression of BORIS in cancers is due to the hypomethylation of its promoter. High expression of BORIS protein and RNA correlates with the tumour size and grade in cancer patients. High percentages of BORIS transcripts were detected in breast, endometrial, prostatic and colon cancer patients. Lower percentages of BORIS were found in patients with melanoma and cancers of the head and neck. The expression of BORIS varied from low to high in lung, colon and ovarian cancer, melanoma and leukaemic cell lines. Lower expressions of BORIS were found in head and neck, breast, kidney, bladder, testicular and prostate carcinoma cell lines. An inhibitor of DNA methylation, 5-aza-2'deoxy-cytidine (5-azadC), and histone deacetylase inhibitors induced or enhanced the expression of BORIS in various carcinoma cell lines. The silencing of BORIS induced apoptosis in tumorous cell lines. BORIS antitumor vaccines have been tested in mice with several cancers, based on the deletion of the DNA-binding ZF-region of the BORIS.
Ruder Bošković Institute, Division of Molecular Medicine, P.O. Box 180, 10002 Zagreb, Croatia. kleiner@irb.hr
Irena
I
Martin-Kleiner
D000818:Animals; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D014158:Transcription, Genetic
C456540:CTCFL protein, human; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins