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Methylation-mediated gene silencing of suppressor of cytokine signaling-1 (SOCS-1) gene in esophageal squamous cell carcinoma patients of Kashmir valley
Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), Noida, India.
Department of Biotechnology, Panjab University, Chandigarh, India.ORCID-id: 0000-0003-2885-5708
Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India.
Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), Noida, India.
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2011 (engelsk)Inngår i: Journal of Receptor and Signal Transduction Research, ISSN 1079-9893, E-ISSN 1532-4281, Vol. 31, nr 2, s. 147-56Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
Informa Healthcare, 2011. Vol. 31, nr 2, s. 147-56
Emneord [en]
SOCS-1, promoter methylation, ESCC
HSV kategori
Forskningsprogram
Naturvetenskap
Identifikatorer
URN: urn:nbn:se:his:diva-8998DOI: 10.3109/10799893.2011.553836ISI: 000288167600007PubMedID: 21385099Scopus ID: 2-s2.0-79952591142OAI: oai:DiVA.org:his-8998DiVA, id: diva2:712821
Tilgjengelig fra: 2014-04-16 Laget: 2014-04-16 Sist oppdatert: 2017-12-05bibliografisk kontrollert

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