Expression of beta-tubulin isotypes in human ovarian carcinoma xenografts and in a sub-panel of human cancer cell lines from the NCI-anticancer drug screen: Correlation with sensitivity to microtubule active agents

Paclitaxel resistance has been associated with overexpression of P-glycopro tein and alterations involving tubulin. To investigate the clinical relevan ce of these in vitro resistance mechanisms, we established 12 human ovarian carcinoma xenografts, using samples from patients before the start of ther apy or after paclitaxel treatment. These xenografts showed a wide range of sensitivity to paclitaxel, and in 4 of them, very low levels of multidrug r esistance-1 expression were detected. Using quantitative PCR and human spec ific primers, the expression of five beta -tubulin isotypes was determined. HM40 was the predominant, accounting for 84.7-98.7% of all tubulin; expres sion of the other four isotypes (H beta9, H beta4, H%beta, and H beta2) was also detected but at lower levels. No correlation could be demonstrated be tween isotype expression and paclitaxel sensitivity in these 12 xenografts. A similar pattern of beta -tubulin isotype expression was observed in a su bset of cell lines from the National Cancer Institute-Anticancer Drug Scree n. In these cell lines, however, a significant correlation between increase d expression of H beta4 isotype and resistance to paclitaxel was found. Tak en together, these results suggest that altered expression of specific R-tu bulin isotypes may not play a significant role in paclitaxel sensitivity in vivo and argue against a possible significance in a clinical setting.