Journal Article

Oncogene regulation of tumor suppressor genes in tumorigenesis

Jimmy Sung, Joel Turner, Susan McCarthy, Steve Enkemann, Chan Gong Li, Perally Yan, Timothy Huang and Timothy J. Yeatman

in Carcinogenesis

Volume 26, issue 2, pages 487-494
Published in print February 2005 | ISSN: 0143-3334
Published online February 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh318
Oncogene regulation of tumor suppressor genes in tumorigenesis

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We attempted to demonstrate whether there is an epigenetic link between oncogenes and tumor suppression genes in tumorigenesis. We designed a high throughput model to identify a candidate group of tumor suppressor genes potentially regulated by oncogenes. Gene expression profiling of mock-transfected versus v-src-transfected 3Y1 rat fibroblasts identified significant overexpression of DNA methyltransferase 1, the enzyme responsible for aberrant genome methylation, in v-src-transfected fibroblasts. Secondary microarray analyses identified a number of candidate tumor suppressor genes that were down-regulated by v-src but were also re-expressed following treatment with 5-aza-2′-deoxycytidine, a potent demethylating agent. This candidate group included both tumor suppressor genes that are known to be silenced by DNA hypermethylation and those that have not been previously identified with promoter hypermethylation. To further validate our model, we identified tsg, a tumor suppressor gene that was shown to be down-regulated by v-src and found to harbor dense promoter hypermethylation. Our model demonstrates a cooperative relationship between oncogenes and tumor suppressor genes mediated through promoter hypermethylation.

Keywords: DAC, 5-aza-2′-deoxycytidine; DNMT1, DNA-cytosine 5-methyltransferase

Journal Article.  4187 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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