Alterations of the P16 gene in uterine cervical carcinoma from Indian patients

Tripathi, Anusri; Banerjee, Soma; Roy, Anup; Roychowdhury, Susanta; Panda, Chinmay Kumar

doi:10.1046/j.1525-1438.2003.13330.x

Cited by 18 publications

(3 citation statements)

References 26 publications

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“…The mutation of EGFR and SH3GL2 was screened in 30 dysplastic lesions, 148 invasive samples and 3 oral cancer cell lines by single strand conformation polymorphism (SSCP) analysis using [α-P32] dCTP as described by Tripathi el al [16].The mutational hotspot region of kinase domain encompassing the exon-18 to exon-21 were selected for mutation analysis of EGFR . For mutation analysis of SH3GL2 , important enzymatic domain and alternating splice site of the gene were selected.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of EGFR in Head and Neck Squamous Cell Carcinoma Is Associated with Inactivation of SH3GL2 and CDC25A Genes

et al. 2013

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The aim of this study is to understand the mechanism of EGFR overexpression in head and neck squamous cell carcinoma (HNSCC). For this reason, expression/mutation of EGFR were analyzed in 30 dysplastic head and neck lesions and 148 HNSCC samples of Indian patients along with 3 HNSCC cell lines. In addition, deletion/methylation/mutation/expression of SH3GL2 (associated with EGFR degradation) and CDC25A (associated with dephosphorylation of EGFR) were analyzed in the same set of samples. Our study revealed high frequency of EGFR overexpression (66–84%), low frequency of gene amplification (10–32.5%) and absence of functional mutation in the dysplastic lesions and HNSCC samples. No correlation was found between protein overexpression and mRNA expression/gene amplification status of EGFR. On the other hand, frequent alterations (deletion/methylation) of SH3GL2 (63–77%) and CDC25A (37–64%) were seen in the dysplastic and HNSCC samples. Two novel single nucleotide polymorphism (SNPs) were found in the promoter region of SH3GL2. Reduced expression of these genes showed concordance with their alterations. Overexpression of EGFR and p-EGFR were significantly associated with reduced expression and alterations of SH3GL2 and CDC25A respectively. In-vitro demethylation experiment by 5-aza-2′-deoxycytidine (5-aza-dC) showed upregulation of SH3GL2 and CDC25A and downregulation of EGFR expression in Hep2 cell line. Poor patient outcome was predicted in the cases with alterations of SH3GL2 and CDC25A in presence of human papilloma virus (HPV) infection. Also, low SH3GL2 and high EGFR expression was a predictor of poor patient survival. Thus, our data suggests that overexpression of EGFR due to its reduced degradation and dephosphorylation is needed for development of HNSCC.

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Section: Methodsmentioning

confidence: 99%

Overexpression of EGFR in Head and Neck Squamous Cell Carcinoma Is Associated with Inactivation of SH3GL2 and CDC25A Genes

et al. 2013

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“…Mutation, hypermethylation, and allelic alteration (loss of heterozygosity (LOH), microsatellite size alteration) of CKDN2A were associated with the development of dysplastic lesions [ 22 , 49 – 52 ]. Particularly, LOH and absence of p16 protein might be associated with the progression of normal mucosa to hyperplastic lesion or carcinoma in situ [ 49 , 53 , 54 ]. Recently, in malignant melanoma a CDKN2A deficient mouse cell line demonstrated MET gene amplification [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Oncogenes and tumor suppressor genes in squamous cell carcinoma of the tongue in young patients

et al. 2015

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ObjectivesThe occurrence of squamous cell carcinoma of the tongue (SCCT) of young patients increased. There are still controversies about patient prognosis. The underlying molecular mechanisms remain unclear.Methods276 patients (66 ≤45, 210 >45 years) with SCCT were included. Clinical parameters and survival data were assessed. Oncogenes and tumor suppressors were analyzed via immunohistochemistry (p53, CXCR4, p16, EGFR) and qPCR (CDK4, CDKN2A, TP53, MDM2, AKT1, PIK3CA, NRAS, HRAS, KRAS, HGF, MET, EGF, ATM, BRCA1, E2F1, FHIT, RUNX3, STK11, BCL2, CTNNB1).ResultsThe median overall survival was 142 (≤45 years) and 34 months (>45 years) (p < 0.0001; HR [95%CI]: 0.37 [0.30–0.58]). Disease specific survival in patients ≤45 years was with 181 months significantly higher than in patients >45 years (p < 0.0001; HR [95%CI]: 0.33 [0.26–0.57]). Immunhistochemistry visualized a comparable expression of analyzed proteins. QPCR demonstrated in patients ≤45 years a higher expression of genes that are associated with carcinogenesis (CTNNB1, STK11, CDKN2A, HGF, MET) as well as tumor suppressors that constitute an enhanced radio-sensitivity (ATM, BRCA1E2F1, FHIT).ConclusionDerogation of the WNT-CTNNB1-STK11 and CDKN2A-HGF-MET pathway can constitute the carcinogenesis, while the higher expression of radio-sensitizers ATM, BRCA1E2F1 and FHIT can explain the better OS/DSS in young patients.

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“…The exon‐18 to 21 of EGFR was selected for mutation analysis as these regions encode the kinase domain, which is involved in the phosphorylation of β‐catenin at the tyrosine 654 position (Miravet et al, 2003; Nakayama et al, 2014). The SSCP analysis was performed by [α‐P32] dCTP using a specific set of primers of the gene for detection of abnormal band shift as demonstrated previously (Table S1; Tripathi, Banerjee, Roy, Roychowdhury, & Panda, 2003). Sequencing of both strands of samples having an abnormal band shift was done using a 3130xl‐Genetic Analyzer (Applied Biosystems) to confirm the mutation.…”

Section: Methodsmentioning

confidence: 99%

Reduction of nuclear Y654‐p‐β‐catenin expression through SH3GL2‐meditated downregulation of EGFR in chemotolerance TNBC: Clinical and prognostic importance

Islam

Dasgupta

Basu

et al. 2020

Journal Cellular Physiology

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Triple negative breast cancer (TNBC) originates from a less differentiated ductal cell of breast, which is less sensitive to chemotherapy. The chemotolerance mechanism of TNBC has not yet been studied in detail. For this reason, molecular profiles (expression/genetic/epigenetic) of Y654‐p‐β‐catenin (active) and its kinase epidermal growth factor receptor (EGFR) along with SH3GL2 (regulator of EGFR homeostasis) were compared between neoadjuvant chemotherapy treated (NACT) and pretherapeutic TNBC samples. Reduced nuclear expression of Y654‐p‐β‐catenin protein with low proliferation index and CD44 prevalence showed concordance with reduced expression of EGFR/Y1045‐p‐EGFR proteins in the NACT samples than the pretherapeutic TNBC samples. Infrequent messenger RNA expression, gene amplification (10–32.5%), and mutation (1%) of EGFR were seen in the TNBC samples irrespective of therapy, suggesting the importance of EGFR protein stabilization in this tumor. The upregulation of SH3GL2 seen in the NACT samples in contrast to the pretherapeutic samples might be due to its promoter hypomethylation, as seen in the quantitative methylation assay. A similar trend of upregulation of SH3GL2 and downregulation of EGFR, Y1045‐p‐EGFR, Y654‐p‐β‐catenin were seen in the MDA‐MB‐231 cell line using antharacycline antitumor drugs (doxorubicin/nogalamycin). The NACT patients with reduced expression of Y654‐p‐β‐catenin and/or EGFR and high expression of SH3GL2 showed comparatively better prognosis than the pretherapeutic patients. Thus, our study showed that reduced nuclear expression of Y654‐p‐β‐catenin in NACT samples due to downregulation of EGFR protein through promoter hypomethylation‐mediated upregulation of SH3GL2, resulting in low proliferation index/CD44 prevalence with better prognosis of the NACT patients, might have an important role in the chemotolerance of TNBC.

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Alterations of the P16 gene in uterine cervical carcinoma from Indian patients

Cited by 18 publications

References 26 publications

Overexpression of EGFR in Head and Neck Squamous Cell Carcinoma Is Associated with Inactivation of SH3GL2 and CDC25A Genes

Overexpression of EGFR in Head and Neck Squamous Cell Carcinoma Is Associated with Inactivation of SH3GL2 and CDC25A Genes

Oncogenes and tumor suppressor genes in squamous cell carcinoma of the tongue in young patients

Reduction of nuclear Y654‐p‐β‐catenin expression through SH3GL2‐meditated downregulation of EGFR in chemotolerance TNBC: Clinical and prognostic importance

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