Aberrant promoter methylation and loss of suppressor of cytokine signalling-1 gene expression in the development of uterine cervical carcinogenesis
2011 (English)In: Cellular Oncology, ISSN 2211-3428, E-ISSN 2211-3436, Vol. 34, no 6, 533-43 p.Article in journal (Refereed) Published
BACKGROUND: Cervical cancer is a leading cause of cancer related deaths in women worldwide caused due to infection of high-risk human papillomaviruses. As JAK/STAT signalling pathway has been shown to play an important role during carcinogenesis, we studied the role of silencing of Suppressor of Cytokine Signalling-1 (SOCS-1) gene, a negative regulator of JAK/STAT pathway in cervical cancer.
METHODS: The expression pattern of SOCS-1 mRNA and protein was analyzed in different stages of cervical tumor biopsies while normal cervical tissues served as controls. RT-PCR, immunohistochemistry and methylation-specific PCR (MSP) were performed to assess the expression pattern and promoter methylation of SOCS-1 gene in a total of 120 fresh surgically resected cervical tissue specimens comprising precancer (n = 12), cancer (n = 78) and normal controls (n = 30).
RESULTS: Compared with expression of SOCS-1 in normal tissues, 64% of the tumor tissues expressed either undetectable or reduced expression. Aberrant promoter methylation of SOCS-1 was found in 61% of the cervical tumor tissues. SOCS-1 expression and methylation were significantly associated with severity of the disease (p < 0.01).
CONCLUSION: We demonstrate for the first time the transcriptional inactivation of SOCS-1 gene due to hypermethylation and synergism with HPV infection which may play an important role in cervical carcinoma.
Place, publisher, year, edition, pages
2011. Vol. 34, no 6, 533-43 p.
Cervical cancer, SOCS-1, HPV, Promoter methylation
Cancer and Oncology
IdentifiersURN: urn:nbn:se:his:diva-8995DOI: 10.1007/s13402-011-0056-2ISI: 000297362500003PubMedID: 21935712ScopusID: 2-s2.0-84861498667OAI: oai:DiVA.org:his-8995DiVA: diva2:712814