Description of paclitaxel resistance-associated genes in ovarian and breast cancer cell lines.

Purpose: To identify genes involved in the paclitaxel resistance phenotype.

Methods: High-density Affymetrix HG-U95Av2 microarrays were used to quantify gene expression in the resulting cell lines, SKOV-3TR, OVCAR8TR and MCF-7TR, and their drug-sensitive parental lines, SKOV-3, OVCAR8 and MCF-7.

Results: Three paclitaxel-resistant human ovarian and breast cancer cell lines were established.

Overexpression of MAGE/GAGE genes in paclitaxel/doxorubicin-resistant human cancer cell lines.

Previous studies directed at identifying paclitaxel resistance genes in a paclitaxel-resistant subclone of the human ovarian cancer cell line SKOV-3 identified a novel cancer testis antigen, Taxol resistance-associated gene 3 (TRAG-3). Because investigation suggested that TRAG-3, located on chromosome Xq28, does not directly participate in the paclitaxel-resistant phenotype, it was hypothesized that TRAG-3 might be linked to a neighboring gene that is directly involved in the drug-resistant phenotype, or alternatively, overexpression of TRAG-3 might be attributable to coregulation with other cancer testis antigens. To distinguish between these two hypotheses, expression of the genes that flank TRAG-3 was evaluated, namely the Centrin 2 gene and several members of the MAGE gene cluster.

Molecular description of evolving paclitaxel resistance in the SKOV-3 human ovarian carcinoma cell line.

Ovarian cancer is currently the most lethal gynecological malignancy in the United States. Although effective therapies exist, the acquisition of multidrug resistance within persisting tumor cells renders curative therapies elusive for the majority of women with ovarian cancer. In an attempt to better define the evolution of paclitaxel resistance, three SKOV-3 sublines were selected during successive rounds of exposure to increasing paclitaxel concentrations.

beta tubulin mutations are rare in human ovarian carcinoma.

Background: The interaction between paclitaxel and its target, beta tubulin, is essential for effective cytotoxicity. Alterations or mutation of beta tubulin have the potential to alter paclitaxel binding and confer a drug resistant phenotype.

Materials And Methods: Twenty-nine paired tumor samples from women with ovarian cancer were examined to evaluate the incidence of exon four mutations in tumors with evolving paclitaxel resistance.

cDNA Technologies and their application to drug resistance research: power, potential and problems.

The effectiveness of systemic chemotherapy is dramatically limited by both intrinsic and acquired drug resistance. Several new technologies have been developed over the last decade to more rapidly identify underlying genetic alterations that impart a drug-resistant phenotype. Techniques such as cDNA-based subtraction technologies, SAGE analysis, and most recently cDNA array and high-density micro-array technologies have rapidly expanded our ability to detect changes in RNA transcription in drug-resistant tumors.