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

J Recept Signal Transduct Res. 2010 Jun;30(3):178-88. doi: 10.3109/10799891003786218.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Expression Regulation, Viral*
  • Humans
  • Immunohistochemistry / methods
  • Middle Aged
  • Papillomaviridae / metabolism*
  • Precancerous Conditions
  • Protein Isoforms
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT5 Transcription Factor / biosynthesis*
  • STAT5 Transcription Factor / chemistry*
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / chemistry*
  • Uterine Cervical Neoplasms / enzymology*
  • Uterine Cervical Neoplasms / metabolism

Substances

  • Protein Isoforms
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • STAT5B protein, human
  • Tumor Suppressor Proteins