Molecular cloning of cervical cancer tumor suppressor gene

点击翻译按钮获取中文摘要

Although cervical carcinoma is caused by infection with certain types of human papillomavirus (HPV) such as types 16 and 18, expression of the E6E7 oncogenes of these HPV is not sufficient for the carcinogenesis. In addition to it, inactivation of some tumor suppressor gene (s) may be indispensable. The objective of this research is to isolate tumor suppressor genes involved in cervical carcinogenesis.We attempted to isolate a gene (s) affecting tumorigenesity of cervical carcinoma-derived cell line (CGL4) by expression cloning using cDNA library prepared from normal human fibroblasts, and obtained a candidate tumor suppressor gene AF337. This gene suppressed growth of tumorigenic CGL4 cells when introduced, that is, AF337 expression vector gave smaller number of drug resistant colonies than control vectors, and almost (23/24), except one (clone 5), colonies appeared did not retain or express the cDNA.The clone 5 formed tumors in nude mice, but the 2 of 3 tumors formed lost the cDNA.The AF337 mRNA was about 2.3kb in size and was expressed in all tissues examined. Expression of this gene was reduced in some cancer cell lines. The predicted gene product was composed of 373 amino acids and possessed highly acidic region, proline-rich domain, and leucine-zipper motif, suggesting that AF337 may be a transcription factor. This gene had no apparent sequence homology with other genes of known function.