Overexpression of y-tubulin in non-small cell lung cancer

• Autores: Nicoletta F. Maounis, Eduarda Dráberová, Eleni Mahera, Maria Chorti, Valentina Caracciolo, Tetyana Sulimenko, Dimitra Riga, Nikolaos Trakas, Aphrodit Emmanouilidou, Antonio Giordano, Pavel Dráber, C. D. Katsetos
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 27, Nº. 9, 2012, págs. 1183-1194
• Idioma: inglés
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  • We and others have previously shown that increased expression and altered compartmentalization of ?-tubulin may contribute to tumorigenesis and tumor progression (J. Cell Physiol. 2009;223:519-529; Cancer Biol. Ther. 2010;9:66-76). Here we have determined by immunohistochemistry the localization and cellular distribution of ?-tubulin in clinical tissue samples from 109 non-small cell lung cancer (NSCLC) cases. The expression and distribution of ?-tubulin protein and transcripts was also determined in the NSCLC tumor cell lines NCI-H460 (HTB-177) and NCI-H69 (HTB-119) by immunocytochemistry, quantitative immunoblotting and reverse transcription quantitative real-time PCR (RT-qPCR). Polyclonal and monoclonal anti-peptide antibodies recognizing epitopes in the C- or N-terminal domains of ?-tubulins and human gene-specific primers for ?-tubulins 1 (TUBG1) and 2 (TUBG2) were used. In non-neoplastic cells of the airway epithelium in situ, ?-tubulin exhibited predominantly apical surface and pericentriolar localizations. In contrast, markedly increased, albeit heterogeneous and variously prominent ?-tubulin immunoreactivity was detected in clinical tumor specimens and in the NCI-H460 and NCI-H69 cell lines, where tumor cells exhibited overlapping multi-punctate and diffuse patterns of localization. Co-expression of ?-tubulin and Ki-67 (MIB-1) was detected in a population of proliferating tumor cells. A statistically significant increase of ?-tubulin expression was found in Stage III compared to lesser stage tumors (p<0.001 v. Stages I/II) regardless of histological subtype or grade. By quantitative immunoblotting NCI-H460 and NCI-H69 cells expressed higher levels of ?-tubulin protein compared to small airway epithelial cells (SAEC). In both tumor cell lines increase in TUBG1 and TUBG2 transcripts was detected by RT-qPCR. Our results reveal for the first time an increased expression of ?-tubulin in lung cancer.