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- Hussain, Showket, et al.
(author)
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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
- 2011
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In: Journal of Receptor and Signal Transduction Research. - : Informa Healthcare. - 1079-9893 .- 1532-4281. ; 31:2, s. 147-56
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Journal article (peer-reviewed)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.
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- Sobti, Ranbir C., et al.
(author)
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Deregulation of STAT-5 isoforms in the development of HPV-mediated cervical carcinogenesis
- 2010
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In: Journal of Receptor and Signal Transduction Research. - : Informa Healthcare. - 1079-9893 .- 1532-4281. ; 30:3, s. 178-188
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Journal article (peer-reviewed)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.
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3. |
- Singh, Neha, et al.
(author)
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Implication of high risk Human papillomavirus HR-HPV infection in prostate cancer in Indian population- A pioneering case-control analysis
- 2015
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5
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Journal article (peer-reviewed)abstract
- Prostate cancer is the second most common cancer with sexual history as a consistent risk factor. This is the pioneering study that evaluates the frequency of HPV infection in prostate cancer in India. Ninety five (95) histopathologically confirmed cancer and fifty five (55) BPH from Indian population were analyzed for HPV infection using a pair of consensus sequence primer followed by type specific PCRs for both high-risk and low-risk HPV types. The data demonstrate HPV infection in 41% of prostate tumor biopsies and 20% in BPH. Subsequent PCR- based HPV typing using type - specific primers revealed 32% were infected with HPV type 16 whereas 6% were found to be positive for HPV type 18, while in BPH controls only 5% of the BPH controls were infected with HPV 16 and this difference was highly significant (p = 0.0004). Significant proportion of HPV infected (74%) cases belonged to stage III and IV (p < 0.001) with a high Gleason score ≥8 (p = 0.003). The study represents for the first time the incidence of HPV infection in prostate cancer in Indian population and strengthens the hypothesis that HPV infection could be one of the co factor associated with progression of prostate cancer.
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4. |
- Singh, Neha, et al.
(author)
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Overexpression of signal transducer and activator of transcription (STAT-3 and STAT-5) transcription factors and alteration of suppressor of cytokine signaling (SOCS-1) protein in prostate cancer
- 2012
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In: Journal of Receptor and Signal Transduction Research. - : Informa Healthcare. - 1079-9893 .- 1532-4281. ; 32:6, s. 321-7
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Journal article (peer-reviewed)abstract
- BACKGROUND: Prostate cancer is a leading cause of mortality in men worldwide especially in developing countries like India. The molecular mechanisms of the oncogenic signaling pathway(s) that are involved in prostate carcinogenesis play a crucial role in disease progression and persistence. There is an important role of signal transducer and activator of transcriptions (STATs) particularly STAT-3 and STAT-5 and its negative regulator suppressor of cytokine signaling-1 (SOCS-1).METHODS: In the present study, the expression and localization of STAT and SOCS-1 proteins in prostate cancer by immunohistochemistry in a total of 150 formalin-fixed, paraffin-embedded human prostate tissues of different grade obtained by radical prostatectomies or transurethral resection.RESULTS: A significantly strong STAT-3 expression pattern in 68% (65/95) prostate cancer cases as compared to 12% (5/55) in benign prostatic hyperplasia (BPH) controls (P < 0.001) was observed. Interestingly the SOCS-1 expression was found to be significantly elevated in prostate cancer cases (P < 0.001).CONCLUSIONS: The present study demonstrates overexpression of STAT-3 and STAT-5 proteins and a contrasting role of SOCS-1 in prostate cancer. These results suggest a critical association between altered expression of STAT-3 and STAT-5 with SOCS-1 and indicate its potential role as a negative regulator independent of JAK-STAT pathway in tumorigenic transformation of prostate tissue. The results of the present report focuses on the fundamental differences in major oncogenic signaling cascades between benign and malignant form of prostate tissue that plays a crucial role in prostate cancer biology.
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5. |
- Sobti, Ranbir Chander, et al.
(author)
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Genetic variants of EGFR (142285G>A) and ESR1 (2014G>A) gene polymorphisms and risk of breast cancer
- 2012
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In: Molecular and Cellular Biochemistry. - : Springer Science+Business Media B.V.. - 0300-8177 .- 1573-4919. ; 369:1-2, s. 217-25
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Journal article (peer-reviewed)abstract
- Breast cancer is one of the most common cancers in women worldwide. The estrogen receptor alpha (ESR1) and epidermal growth factor receptor (EGFR) have been known to play a vital role in development and progression of breast cancer. The aim of the present study was to determine the relationship, if any, between genetic polymorphism in (ESR1) 2014G>A (T594T) and (EGFR) 142285G>A (R521K) with risk of breast cancer and the prognosis in a heterogeneous North Indian population that is known for its diverse ethnicity. A case-control study in a total of 300 individuals comprising of 150 breast cancer patients and 150 normal controls was performed. PCR-RFLP was employed for genotyping. The G/A heterozygous genotype EGFR R521K, was slightly higher in cases (56.7 %) than in controls (48.3 %) (P = 0.20). The results indicated that EGFR polymorphism does not show any significant association with breast cancer in this population. On the other hand, the mutant A/A genotype ESR1 codon 594, showed a 6.4-folds risk for breast cancer and this association was highly significant (P = 0.00) as compared to wild GG genotype, the heterozygous G/A genotype also showed a significant association with disease (P = 0.00, OR = 2.03). In addition, the frequency of A allele was also higher in cases (36 %) than in controls (19 %) and a highly significant difference was observed with wild G allele (63.3 % in cases and 6.6 % in controls). This clearly indicates that there appears to be an influence of ESR1 codon 594 genotypes on genetic susceptibility to breast cancer. Further a significantly higher risk was observed in individuals who had diabetes {OR = 3.04 (1.68-5.50), P = 0.00} and females with ESR polymorphism in pre-menopause patients that had undergone menopause above the age of 50 years {OR = 3.58 (1.86-6.90), P < 0.05}. The different ethnic backgrounds and geographical locations have complimented the present genotypic analysis and have highlighted the influence of ethnicity, race and geographic location in genetic predisposition to breast cancer.
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