Deregulation of STAT-5 isoforms in the development of HPV-mediated cervical carcinogenesis

Abstract

Background: Cervical cancer is the second most common cancer and is leading cause of cancer related deaths in women worldwide. High Risk-Human papillomavirus (HPV) types play an important role in cervical carcinogenesis. Considering the important role of signal transducer and activator of transcription-5 (STAT-5), an important member of JAK/STAT family which plays a crucial role in various cancers and HPV as a key mediator in the development of cervical carcinogenesis, the purpose of the current study was to examine the possible relationship between HPV infection and expression of STAT-5 gene isoforms in cervical cancer. Methods: A total of 120 fresh cervical tissue specimens comprising precancer (n=12), cancer (n=78) and normal controls (n=30) were analyzed for HPV infection and expression pattern of STAT-5 mRNA (both isoforms STAT-5a and STAT-5b) and protein in different stages of cervical carcinoma biopsies by reverse-transcriptase-PCR, western blotting and immunohistochemistry. Results: A significantly increased expression of STAT-5 was detected in most of the cervical tumors (P < 0.001), whereas it was almost undetectable in normal controls. Also the study of relative contribution of STAT-5 isoforms revealed a higher expression pattern of STAT-5b and was associated with severity of the disease. On the contrary, STAT-5a was found to be significantly downregulated in cervical tumor tissues (P < 0.001). HPV infection was found in 90% of the cervical cancer cases and was significantly associated with STAT-5 overexpression (P=0.001). Conclusions: We observed for the first time the differential expression pattern of STAT-5 isoforms in cervical cancer and that STAT-5 may play an important role in the progression of HPV-mediated cervical cancer.