Abstract
BackgroundDespite 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.MethodsUsing 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.ResultsWe 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.ConclusionsWe 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.
Highlights
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
In this paper we report that in HNSCC samples both the Messenger ribonucleic acid (mRNA) and protein levels of Tbx3 are increased with respect to their normal tissue counterparts, whereas phosphatase and TENsin Homolog (PTEN) mRNA levels are decreased in cancer tissues as it has been reported before [33]
In order to determine whether the increase in Tbx3 mRNA level correlates with protein level in HNSCC tissue samples, paraffin embedded cancer and normal tissue sections were stained with anti-Tbx3 antibody
Summary
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. We hypothesize that Tbx may be over expressed in HNSCC and may repress PTEN, leading to cancer formation and/or progression. Tbx transcription factors family plays important roles in cell proliferation, fate and identity during development [2,3]. Based on their development and various abnormalities of the heart and genitalia [8]. FGF signalling regulates Tbx3 [15] and Tbx cooperates with c-Myc and Ras associated transformation [16,17]. Repression of p14/19ARF or p21Cip1/WAF1 by Tbx seems to block this protective pathway and bypass cellular senescence via p53 dependent or independent ways, leading to uncontrolled cell proliferation. In the light of the available evidence, it seems that Tbx uses multiple pathways and mechanisms in driving tumorigenesis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
