Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes.

This is the first report of altered expression of specific ␤-tubulin genes in taxol-resistant ovarian tumors and we propose that the latter may play a role in clinical resistance to taxol. (J

M Kavallaris

2008

Scholarcy highlights

  • Ovarian cancer is the leading cause of death from gynecological malignancies in the United States
  • This is the first report of altered expression of specific ␤-tubulin genes in taxol-resistant ovarian tumors and indicates that clinical resistance to taxol may be associated with enhanced expression of specific ␤-tubulin isotypes
  • By developing a highly specific PCR procedure we were able to examine the expression of individual ␤-tubulin genes in both sensitive and taxol-resistant lung cancer cell lines
  • We demonstrated for the first time that clinically derived taxol-resistant ovarian epithelial tumor cells display increased expression of specific ␤-tubulin genes compared with primary untreated tumors
  • Having demonstrated that specific ␤-tubulin changes are associated with taxol resistance in laboratory-derived cell lines, it was important to determine whether similar changes in expression occurred in taxol-refractory ovarian tumors
  • Drug resistance is often a multifactorial process and we cannot exclude the possibility that mechanisms distinct from ␤-tubulin isotype changes are contributing to taxol resistance, we provide evidence that expression of ␤-tubulin isotypes HM40, H␤4, and H5␤ is increased in taxol-resistant cell lines and human tumors
  • Improved understanding of the way in which ␤-tubulin isotype expression is altered, and the effect it has on microtubule dynamics in response to taxol treatment in human tumors could assist in the development of strategies to circumvent resistance

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