Deregulation of STAT-5 isoforms in the development of HPV-mediated cervical carcinogenesis.
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.
Sobti
Ranbir C
RC
Department of Biotechnology, Panjab University, Sector-14, Chandigarh, India. rcsobti@pu.ac.in
Singh
Neha
N
Hussain
Showket
S
Suri
Vanita
V
Bharadwaj
Mausumi
M
Das
Bhudev C
BC
D000328:Adult; D001706:Biopsy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D027383:Papillomaviridae / Q000378:metabolism*; D011230:Precancerous Conditions; D020033:Protein Isoforms; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000096:biosynthesis* / Q000737:chemistry*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000378:metabolism
D020033:Protein Isoforms; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; D025521:Tumor Suppressor Proteins