CpG methylation inactivates the promoter activity of the human retinoblastoma tumor-suppressor gene - PubMed (original) (raw)
Affiliations
- PMID: 8455933
CpG methylation inactivates the promoter activity of the human retinoblastoma tumor-suppressor gene
N Ohtani-Fujita et al. Oncogene. 1993 Apr.
Abstract
Cytosine methylation of CpG sites in the promoter region of eucaryotic genes is involved in the inactivation of expression of certain genes. Given that methylation can lead to reduced transcription, it is possible that expression of tumor-suppressor genes is also inactivated by hypermethylation, thereby contributing to the etiology of cancer. Recently we found five sporadic retinoblastoma tumors (16% of all unilateral cases) with hypermethylation of the 5' end of the retinoblastoma gene without detecting any structural abnormalities. However, it is unclear whether the promoter of the retinoblastoma gene is actually inactivated by its hypermethylation. Here we show that specific hypermethylation in the promoter region of the retinoblastoma gene reduces its expression to only 8% of the unmethylated control. Furthermore, we have found that two transcription factors important for the promoter activity, an activating transcription factor (ATF)-like factor and the retinoblastoma binding factor 1, do not bind when their recognition sequences are CpG methylated. These results in vitro strongly support the hypothesis that CpG methylation of the human tumor-suppressor gene can result in the inactivation of the gene and thus lead to oncogenesis.
Similar articles
- Extensive DNA methylation spanning the Rb promoter in retinoblastoma tumors.
Stirzaker C, Millar DS, Paul CL, Warnecke PM, Harrison J, Vincent PC, Frommer M, Clark SJ. Stirzaker C, et al. Cancer Res. 1997 Jun 1;57(11):2229-37. Cancer Res. 1997. PMID: 9187126 - Effects of methylation of non-CpG sequence in the promoter region on the expression of human synaptotagmin XI (syt11).
Inoue S, Oishi M. Inoue S, et al. Gene. 2005 Mar 28;348:123-34. doi: 10.1016/j.gene.2004.12.044. Gene. 2005. PMID: 15777718 - CpG methylation inactivates the transcriptional activity of the promoter of the human p53 tumor suppressor gene.
Schroeder M, Mass MJ. Schroeder M, et al. Biochem Biophys Res Commun. 1997 Jun 18;235(2):403-6. doi: 10.1006/bbrc.1997.6796. Biochem Biophys Res Commun. 1997. PMID: 9199206 - [Molecular cancer epidemiology--the present status and future possibilities].
Sakai T. Sakai T. Nihon Eiseigaku Zasshi. 1996 Feb;50(6):1036-46. doi: 10.1265/jjh.50.1036. Nihon Eiseigaku Zasshi. 1996. PMID: 8720930 Review. Japanese. - Diverse mutations lead to inactivation of the retinoblastoma gene.
Lee EY, Huang S, Shew JY, Donoso LA, Lee WH. Lee EY, et al. Prog Clin Biol Res. 1991;362:221-40. Prog Clin Biol Res. 1991. PMID: 2003126 Review. No abstract available.
Cited by
- CmC(A/T)GG DNA methylation in mature B cell lymphoma gene silencing.
Malone CS, Miner MD, Doerr JR, Jackson JP, Jacobsen SE, Wall R, Teitell M. Malone CS, et al. Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10404-9. doi: 10.1073/pnas.181206898. Epub 2001 Aug 14. Proc Natl Acad Sci U S A. 2001. PMID: 11504918 Free PMC article. - Knudson to embryo selection: A story of the genetics of retinoblastoma.
Athavale V, Khetan V. Athavale V, et al. Taiwan J Ophthalmol. 2018 Oct-Dec;8(4):196-204. doi: 10.4103/tjo.tjo_37_18. Taiwan J Ophthalmol. 2018. PMID: 30637191 Free PMC article. Review. - CpG methylation as a mechanism for the regulation of E2F activity.
Campanero MR, Armstrong MI, Flemington EK. Campanero MR, et al. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6481-6. doi: 10.1073/pnas.100340697. Proc Natl Acad Sci U S A. 2000. PMID: 10823896 Free PMC article. - The two-hit theory hits 50.
Chernoff J. Chernoff J. Mol Biol Cell. 2021 Dec 1;32(22):rt1. doi: 10.1091/mbc.E21-08-0407. Mol Biol Cell. 2021. PMID: 34735271 Free PMC article. - Absence of methylation of CpG dinucleotides within the promoter of the breast cancer susceptibility gene BRCA2 in normal tissues and in breast and ovarian cancers.
Collins N, Wooster R, Stratton MR. Collins N, et al. Br J Cancer. 1997;76(9):1150-6. doi: 10.1038/bjc.1997.526. Br J Cancer. 1997. PMID: 9365162 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources