Epigenetic and genetic loss of Hic1 function accentuates the role of p53 in tumorigenesis Journal Article
| Authors: | Chen, W.; Cooper, T. K.; Zahnow, C. A.; Overholtzer, M.; Zhao, Z.; Ladanyi, M.; Karp, J. E.; Gokgoz, N.; Wunder, J. S.; Andrulis, I. L.; Levine, A. J.; Mankowski, J. L.; Baylin, S. B. |
| Article Title: | Epigenetic and genetic loss of Hic1 function accentuates the role of p53 in tumorigenesis |
| Abstract: | The gene hypermethylated in cancer 1 (HIC1) is epigenetically inactivated, but not mutated, in cancer. Here we show that cooperative loss of Hic1 with p53, but not INK4a, yields distinct tumor phenotypes in mice. Germline deletion of one allele of each gene on the opposite chromosome yields breast and ovarian carcinomas and metastatic osteosarcomas with epigenetic inactivation of the wild-type Hic1 allele. Germline deletion of the two genes on the same chromosome results in earlier appearance and increased prevalence and aggressiveness of osteosarcomas with genetic deletion of both wild-type genes. In human osteosarcomas, hypermethylation of HIC1 is frequent only in tumors with p53 mutations. Our results indicate the importance of genes altered only through epigenetic mechanisms in cancer progression in conjunction with genetically modified tumor suppressor genes. |
| Keywords: | immunohistochemistry; osteosarcoma; controlled study; human cell; methylation; gene deletion; mutation; nonhuman; cancer incidence; chromosome; mouse; phenotype; animals; mice; mice, knockout; allele; animal tissue; gene; metastasis; ovary cancer; breast cancer; animal experiment; animal model; gene function; heterozygote; wild type; protein p53; dna methylation; carcinogenesis; animalia; transcription factors; cell transformation, neoplastic; cancer invasion; epigenetics; epigenesis, genetic; neoplasm metastasis; tumor suppressor protein p53; gene loss; gene inactivation; cyclin-dependent kinase inhibitor p16; chromosome deletion; genes, tumor suppressor; promoter regions (genetics); humans; human; priority journal; article; hypermethylated in cancer 1 gene |
| Journal Title: | Cancer Cell |
| Volume: | 6 |
| Issue: | 4 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2004-10-01 |
| Start Page: | 387 |
| End Page: | 398 |
| Language: | English |
| DOI: | 10.1016/j.ccr.2004.08.030 |
| PROVIDER: | scopus |
| PUBMED: | 15488761 |
| DOI/URL: | |
| Notes: | Cancer Cell -- Cited By (since 1996):88 -- Export Date: 16 June 2014 -- CODEN: CCAEC -- Source: Scopus |
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