Expression And Clinical Significances Of RASSF1A Gene In Cervical Cancer

PrefaceThe uterine cervical carcinomal is one of the most common malignant tumors in women,the mortality of the disease has been keeping highly. Oncomo-lecularbiology indicates that the development of cervical cancer due to oncogene being activated and anti - oncogene being inactivated.Recently, Dammann et al. indentified and cloned a gene from the common homozygous deletion area at 3p21.3. this gene,named RASSF1A(RAS association domain family protein 1A) ,has homology to mammalian RAS effectors. Although little is known about the function of RASSF1A, it has been shown to dramatically reduce tumorigenicity in vivo. RASSF1A is frequently inactivated in a variety of primary human cancers. On the basis of these observations, we testd whether epigenetis silencing of RASSF1A play a role in the development of cervical cancer and explored the relationship with HPV - 16 in cervial cancer.Materials and Methods56 samples of invasive cervical carcinoma, 36 samples of CIN and 20 ones of normal cervix were collected from the second Affiliated Hospital of China Medical University.RT - PCR system was used for detection of the RASSF1A, each cases was also analyzed for the presence of oncogenic HPV - 16 DNA using a PCR -based method.Statistical analysis was performed using SPSS for windows 11.0 sofeware. Comparisons were made by X~2 test and Fisher's exact test. The relationship of RASSF1A and HPV - 16 was made by rank sum test. P <0.05 have statisticalsignificance.ResultsThe loss of RASSFIA mRNA expression was respectively 0% (0/20) ,22. 2% (8/36) and 50.0% (28/56) in patients with normal cervix ,CIN and cervical cancer . Loss of RASSFIA mRNA in advanced stage(82. 4% ) was higher than in early stage (35.9% ) (P <0.05) in cervical cancers, RASSFIA mRNA deletion occurred more often in squamous cervical cancers(63. 3% ) than in ad-enocarcinomas (34.6% ) (P <0.05). High frequency of RASSFIA mRNA loss could be found in poor differentiation group (P <0.05). The loss of RASSFIA has negative relationship with HPV -16 infection in cervical cancers, especially in adenocarcinomas.DiscussionRASSFIA is frequently inactivated in a variety of primary human tumors. In our study, we demonstrate RASSF1A frequent inactivation in cervial cancer, some cases are absent in CIN and no is absent in normal cases. Loss of RASSFIA mRNA in advanced stage was higher than in early stage in cervical cancer. The result demonstrate RASSF1A as a tumor suppressive gene play an important role in the development of cervical cancer.Understanging the relationship between HPV infection and RASSFIA inactivation is important in cervical cancer, as well as in other HPV - related tumors. RASSFIA blocks cell cycle checkpoint and inhibits cyclin Dl accumulation . Bypassing the Rb family, dependent cell cycle checkpoint E7 papillomavir-us protein can overcome RASSFIA -induced cell cycle arrest. The observed inverse correlation between HPV -16 infection and RASSFIA absence in cervical cancers could reflect a functional interaction between the cellular RASSFIA and viral E6/E7 protein. The interaction could play an important role in both neo-plastic transformation and immortalization of cervical epithelial cells.ConclusionsLoss of RASSFl A may play an important role in tumorgenesis and development of cervical cancer. RASSFl A may as an index appraise the prognosis of patients with cervical cancer.