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Cited by 52Head and Neck Cancer StudiesPI3K/AKT/mTOR signaling in cancerCancer-related molecular mechanisms research

Tbx3 represses PTEN and is over-expressed in head and neck squamous cell carcinoma

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Burgucu, Durmus, Guney, Kenan, Sahinturk, Duygu, Ozbudak, Irem Hicran, Ozel, Deniz, Ozbilim, Gulay, Yavuzer, Ugur·2012·BMC Cancer
DOI 10.1186/1471-2407-12-481PMC PMC3517435
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Abstract

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<0.001), whereas PTEN mRNA levels are significantly reduced in cancer tissues. Moreover, Tbx3 protein is also increased in HNSCC tissue sections. Over-expression of Tbx3 in HeLa and HEK cell lines causes reduction in endogenous PTEN mRNA and protein levels. In addition, transcription activity assays reveal that Tbx3 is capable of repressing both the basal and induced promoter activity of PTEN. 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.

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Cited by

Sorted by citations

Authors
Burgucu, D., Guney, K., Sahinturk, D., Ozbudak, I. H., Ozel, D., Ozbilim, G., & Yavuzer, U.
Affiliations
Akdeniz University (TR)
Corresponding author
Yavuzer, Ugur
Venue
BMC Cancer
Publisher
Springer Science and Business Media LLC
Published
2012-10-19
Volume
12
Issue
1
Pages
481-481
ISSN
1471-2407 (ISSN-L)
DOI
10.1186/1471-2407-12-481
PMC
PMC3517435
OpenAlex
W2157244641
Cited by
52
References
4
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 8 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 5 · 2013: 3
FWCI
3.74
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Cancer (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ludwig Institute for Cancer Research
  • Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (109S348)
Topics
  • Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
TBX3, PTEN, head and neck squamous cell carcinoma, transcriptional repression, oncogenes, tumour suppressor, gene overexpression, biomarkers
MeSH terms
Carcinoma, Squamous Cell, Flow Cytometry, Head and Neck Neoplasms, HeLa Cells, Humans, Immunohistochemistry, Promoter Regions, Genetic, Transcription, Genetic, Transfection, Biomarkers, Tumor, Immunoblotting, Gene Expression Regulation, Neoplastic, Reverse Transcriptase Polymerase Chain Reaction, T-Box Domain Proteins, PTEN Phosphohydrolase, HEK293 Cells

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