Preliminary Study On STAT2 Significance In Cervical Carcinogenesis

Signal transducer and activator of transcription 2 (STAT2) is a member of STAT family that plays an important role in natural immunity, anti-virus, proliferation and apoptosis etc. It was reported that by being exposed to a chemical carcinogenesis regimen for stimulation of cancer development, loss of STAT2 gene actually reduced the numbers of tumors in target tissues. Following the chemical treatment in the colon, STAT2 knock-out (KO) mice lost less weight than their wild type counterparts. Likewise, wild type animals developed more, larger tumors and destruction of the normal colon architecture than the STAT2 KO mice. By the end of the 16-week after the treatment,60 percent of the wild type animals had succumbed to cancer while all the STAT2 KO mice survived. These data indicated that STAT2 works as a promoter of tumorigenesis rather than an inhibitor. However, the role of STAT2 in carcinogenesis is unclear.Objects:â‘ To investigate STAT2 expression in tumor tissues and tumor cell lines;â‘¡To study the correlation between STAT2 expression and clinicopathological parameters as well as survival in cervical cancer patients;â‘¢To study the biological functions of STAT2 in cervical tumor cell line, Hela.Methods:â‘ The expression patterns of STAT2 in normal tissues and tumor tissues were forecasted and analyzed by bioinformatics;â‘¡STAT2 expression in several tumor cell lines were investigated assayed by semi-quantitative-RT-PCR to confirm the results from bioinformatics;â‘¢The expression pattern of STAT2 in lesions of the uterine cervix was examined by immunohistochemistry and the correlation between STAT2 expression and clinicpathological parameters as well as patients survival were also analyzed;â‘£The plasmid of STAT2 shRNA or scrambled control was transfected into cervical cancer cell line Hela in order to establish stable cell lines. By using these cell lines, the biological functions of STAT2 in vitro was studied assayed by XTT and colony-formation in soft agar. Stable cell lines were injected into nude mice to analysis functions of STAT2 in vivo.Results:â‘ It was suggested that many cancer cell lines as well as cancer tissues expressed STAT2 by bioinformatics.â‘¡STAT2 was expressed in many tumor cell lines;â‘¢Beginning from mild dysplasia stage, STAT2 was expressed in cervical epithelial cells. The expression was increased paralleled with the transformation. However, STAT2 expression is not associated with tumor prognosis.â‘£The stable cell line psi-STAT2-Hela whose STAT2 gene was silenced showed slower growth rate assayed by XTT and less colony-formation efficiency in soft agar, compared to control cell lines. Nude mice which were injected with psi-STAT2-Hela cells showed smaller tumor size and lower growth rate than control cells.Conclusions:â‘ STAT2 was expressed in most of tumor cell lines and tumor tissues;â‘¡The expression of STAT2 is associated with cervical transformation stages but not with prognosis which suggested that the expression of STAT2 is an early molecular event in cervical carcinogenesis;â‘¢The shRNA of STAT2 inhibited the proliferation of Hela in vivo and in vitro, indicating that the shRNA of STAT2 partly inhibited the malignant phenotypes of cervical tumor cells. It was suggested that STAT2 may be correlated with the malignant behavior of tumor cells.