Tbx3 represses PTEN and is over-expressed in head and neck squamous cell carcinoma
Autor: | Ugur Yavuzer, Durmuş Burgucu, Kenan Güney, Irem Hicran Ozbudak, Duygu Sahinturk, Deniz Ozel, Gulay Ozbilim |
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Rok vydání: | 2012 |
Předmět: |
PTEN
Cancer Research Transcription Genetic Immunoblotting Repressor Transfection lcsh:RC254-282 Flow cytometry HeLa 03 medical and health sciences 0302 clinical medicine Squamous cell carcinoma Biomarkers Tumor Genetics medicine Humans Promoter Regions Genetic Cancer 030304 developmental biology 0303 health sciences biology medicine.diagnostic_test Oncogene Reverse Transcriptase Polymerase Chain Reaction HEK 293 cells PTEN Phosphohydrolase Tbx3 Flow Cytometry lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens biology.organism_classification medicine.disease Immunohistochemistry Molecular biology Head and neck squamous-cell carcinoma 3. Good health Gene Expression Regulation Neoplastic stomatognathic diseases HEK293 Cells Real-time polymerase chain reaction Oncology Head and Neck Neoplasms 030220 oncology & carcinogenesis Carcinoma Squamous Cell Cancer research biology.protein T-Box Domain Proteins Research Article HeLa Cells |
Zdroj: | BMC Cancer, Vol 12, Iss 1, p 481 (2012) BMC Cancer |
ISSN: | 1471-2407 |
DOI: | 10.1186/1471-2407-12-481 |
Popis: | Background Despite advances in diagnostic and treatment strategies, head and neck squamous cell cancer (HNSCC) constitutes one of the worst cancer types in terms of prognosis. PTEN is one of the tumour suppressors whose expression and/or activity have been found to be reduced in HNSCC, with rather low rates of mutations within the PTEN gene (6-8%). We reasoned that low expression levels of PTEN might be due to a transcriptional repression governed by an oncogene. Tbx2 and Tbx3, both of which are transcriptional repressors, have been found to be amplified or over-expressed in various cancer types. Thus, we hypothesize that Tbx3 may be over expressed in HNSCC and may repress PTEN, thus leading to cancer formation and/or progression. Methods Using immunohistochemistry and quantitative PCR (qPCR), protein and mRNA levels of PTEN and Tbx3 were identified in samples excised from cancerous and adjacent normal tissues from 33 patients who were diagnosed with HNSCC. In addition, HeLa and HEK cell lines were transfected with a Tbx3 expressing plasmid and endogenous PTEN mRNA and protein levels were determined via qPCR and flow cytometry. Transcription assays were performed to demonstrate effects of Tbx3 on PTEN promoter activity. Mann–Whitney, Spearman’s Correlation and Wilcoxon signed-rank tests were used to analyze the data. Results We demonstrate that in HNSCC samples, Tbx3 mRNA levels are increased with respect to their normal tissue counterparts (p Conclusions We show that Tbx3 is up-regulated in tissue samples of HNSCC patients and that Tbx3 represses PTEN transcription. Thus, our data not only reveals a new mechanism that may be important in cancer formation, but also suggests that Tbx3 can be used as a potential biomarker in cancer. |
Databáze: | OpenAIRE |
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