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.

Keywords::

• Cervical cancer
• HPV
• STAT-5

Acknowledgements

This study was funded by DBT (Department of Biotechnology), Government of India, New Delhi, India. Fellowship support to N.S. by DBT. We also greatly acknowledge the help done by the staff and patients of Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh. R.C.S. senior scientist who oversaw and guaranteed the work. N.S. and S.H. collected the samples and carried out the experiments and primary manuscript writing. V.S. senior Gynecologist who provided clinical samples and critical revision of manuscript. M.B. conceived and participated in the study and critical revision of the manuscript. B.C.D. who oversaw and gave critical inputs. All authors read and approved the final manuscript.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.