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Cancer Res. 2010 Jun 15;70(12):4995-5003. doi: 10.1158/0008-5472.CAN-09-4487. Epub 2010 May 25.

betaIII-tubulin is a multifunctional protein involved in drug sensitivity and tumorigenesis in non-small cell lung cancer.

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1
Children's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Randwick, New South Wales, Australia.

Abstract

Advanced non-small cell lung cancer (NSCLC) has a dismal prognosis. betaIII-Tubulin, a protein highly expressed in neuronal cells, is strongly associated with drug-refractory and aggressive NSCLC. To date, the role of this protein in in vivo drug resistance and tumorigenesis has not been determined. NSCLC cells stably expressing betaIII-tubulin short hairpin RNA displayed reduced growth and increased chemotherapy sensitivity when compared with control clones. In concordance with these results, stable suppression of betaIII-tubulin reduced the incidence and significantly delayed the growth of tumors in mice relative to controls. Our findings indicate that betaIII-tubulin mediates not only drug sensitivity but also the incidence and progression of lung cancer. betaIII-Tubulin is a cellular survival factor that, when suppressed, sensitizes cells to chemotherapy via enhanced apoptosis induction and decreased tumorigenesis. Findings establish that upregulation of a neuronal tubulin isotype is a key contributor to tumor progression and drug sensitivity in lung adenocarcinoma.

PMID:
20501838
DOI:
10.1158/0008-5472.CAN-09-4487
[Indexed for MEDLINE]
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