Methylation-mediated gene silencing of suppressor of cytokine signaling-1 (SOCS-1) gene in esophageal squamous cell carcinoma patients of Kashmir valley

Hussain, Showket ; Singh, Neha ; Salam, Irfana ; Bandil, Kapil ; Yuvaraj, M. ; Bhat, Mohammad Akbar ; Mir, Mohammad Muzaffar ; Siddiqi, Mushtaq A. ; Sobti, Ranbir C. ; Bharadwaj, Mausumi ; Das, Bhudev C. (2011) Methylation-mediated gene silencing of suppressor of cytokine signaling-1 (SOCS-1) gene in esophageal squamous cell carcinoma patients of Kashmir valley Journal of Receptors and Signal Transduction Research, 31 (2). pp. 147-156. ISSN 1079-9893

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Official URL: http://informahealthcare.com/doi/abs/10.3109/10799...

Related URL: http://dx.doi.org/10.3109/10799893.2011.553836

Abstract

Context: Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths in Jammu and Kashmir. The negative regulation of tumor suppressor gene leading to change in signaling pathway is one of the major mechanisms responsible for tumorigenic transformation. Objective: In the present study, the role of silencing of suppressor of cytokine signaling-1 (SOCS-1) gene, a negative regulator of JAK/STAT pathway, was analyzed in ESCC. Methods: The expression pattern of SOCS-1 gene was analyzed in esophageal tumor biopsies although normal adjacent tissues that served as controls. Reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry, methylation-specific PCR (MSP), and human papillomavirus (HPV) detection were performed to assess the expression pattern and promoter methylation of SOCS-1 gene including HPV status in a total of 75 surgically resected tissue specimens. Results: Compared with the level of SOCS-1 expression in normal tissues, 53% (40/75) of the tumor tissues expressed either undetectable or reduced SOCS-1 expression (>50% loss of expression), which was significantly associated with advanced clinical stage or severe histopathological grade of the disease (P<0.01). Aberrant promoter methylation of the SOCS-1 gene was found in 45% (34/75) of the esophageal tumor tissues, which was also found to be significantly associated with advanced stage of esophageal carcinoma (P<0.01). The prevalence of HPV infection was found in 19% of tumor cases, whereas no HPV could be detected in any of the normal adjacent tissues. Conclusion: Transcriptional inactivation of SOCS-1 gene, primarily due to its promoter hypermethylation although HPV infection, may play an important role in esophageal carcinogenesis in Kashmir.

Item Type:Article
Source:Copyright of this article belongs to Informa plc.
Keywords:SOCS-1; Promoter Methylation; ESCC
ID Code:68404
Deposited On:07 Nov 2011 04:26
Last Modified:07 Nov 2011 04:26

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