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.

Our study results suggest that the distribution of patient age-sex, tumor location, pathologic diagnosis, and postoperative complication rate is consistent with the literature.

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Reactive oxygen metabolites are products of oxidative metabolism that are continuously generated in vivo, and are known to produce serious cellular, tissue and genomic damage. l-carnitine is an endogenous amine that has been shown to have an effect on the synthesis of reactive oxygen metabolites. Twenty Wistar rats, 24 months of age, were randomly assigned to two groups as control and l-carnitine treatment groups. One millilitre of distilled water was administered to control rats and 50 mg/kg l-carnitine to rats of l-carnitine treatment groups by intragastric gavage once a day for 30 days. At the end of 30 days, all groups underwent auditory brainstem response testing after administration of intraperitoneal urethane anaesthesia. l-carnitine treatment reduced III, V latencies and I-III, III-V and I-V interpeak latencies (IPL) significantly compared with the control group. l-carnitine treatment improved age-related deterioration in auditory pathways and hence may be a new alternative for the treatment of presbyacusis.