Journal article

Publication year: 2003

Pages: 1888-1893

Journal: Cancer Research

Volume number: 63

Issue number: 8

ISSN: 0008-5472

eISSN: 1538-7445

URL: http://cancerres.aacrjournals.org/content/63/8/1888

Publisher: American Association for Cancer Research

Abstract: 
Recently, we have identified a new putative tumor suppressor gene, RASSF1A (Ras association domain family 1A gene), located at human chromosome 3p21.3, the segment that is often lost in many types of human cancers. The RASSF1A promoter was shown to be frequently hypermethylated in various epithelial tumors, including small cell lung, breast, bladder, prostate, gastric, and renal cell carcinomas. In this study, we have analyzed the methylation status of the RASSF1A gene in primary human cervical cancers and in eight cervical cancer cell lines. The RASSF1A promoter is hypermethylated in 4 of 42 (= 10%) of squamous cell carcinomas, in 4 of 19 (= 21%) of adenosquamous carcinomas, and in 8 of 34 I(= 24%) of cervical adenocarcinomas. Although in adenocarcinomas, methylation of RASSF1A and presence of human papillomavirus (HPV) type 16 or 18 sometimes coexisted, not a single case of HPV-16/18-positive squamous cell carcinomas had RASSF1A methylation. Similarly, in all eight analyzed cervical cell lines, RASSF1A inactivation and HPV infection were mutually exclusive (Fisher's exact test; P = 0.0357): two HPV-negative cervical cancer cell lines had a methylated and silenced RASSF1A promoter (C-33A and HT-3), whereas the other six HPV-positive lines expressed RASSF1A mRNA (ME 180, MS751, SiHa, C-4I, HeLa, and CaSki). For cervical tumors and cell lines combined, the Pearson's chi(2) test (chi(2) = 3.99; P less than or equal to 0.05) indicates a borderline-significant reverse correlation between inactivation of RASSF1A and the presence of high-risk HPVs. Our data imply that the presence of HPVs in cervical carcinomas alleviates the requirement for RASSF1A inactivation and suggests that these two events may engage the same tumorigenic pathway.

Harvard Citation style: Kuzmin, I., Liu, L., Dammann, R., Geil, L., Stanbridge, E., Wilczynski, S., et al. (2003) Inactivation of RAS association domain family 1A gene in cervical carcinomas and the role of human papillomavirus infection, Cancer Research, 63(8), pp. 1888-1893. http://cancerres.aacrjournals.org/content/63/8/1888

APA Citation style: Kuzmin, I., Liu, L., Dammann, R., Geil, L., Stanbridge, E., Wilczynski, S., Lerman, M., & Pfeifer, G. (2003). Inactivation of RAS association domain family 1A gene in cervical carcinomas and the role of human papillomavirus infection. Cancer Research. 63(8), 1888-1893. http://cancerres.aacrjournals.org/content/63/8/1888