Transcriptome changes induced by docetaxel in human mammary cell lines expressing different levels of ERBB2

Autor(es)

Dos Santos, M. L. ^[1] ; Gimenes, K. P. ^[1] ; Silva, Jr., W. A. ^[2] ; Nagai, M. A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Disciplina Oncol, Dept Radiol, Fac Med, BR-01246903 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Genet, Fac Med Ribeirao Preto, BR-14049 Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Molecular Medicine; v. 23, n. 6, p. 733-743, JUN 2009.
• Citações Web of Science: 6

Resumo

The taxane docetaxel is currently the most effective chemotherapeutic drug for the treatment of advanced breast cancer. However, a considerable proportion of breast cancer patients do not respond positively to docetaxel. The mechanisms of docetaxel resistance are poorly understood. Overexpression of ERBB2 occurs in 15-30% of breast tumors and is associated with chemoresistance to a variety of anticancer drugs. In the present study, we sought to identify genes involved in ERBB2-mediated chemoresistance to docetaxel. We generated SAGE libraries from two human mammary cell lines expressing basal (HB4a) and high (C5.2) levels of ERBB2 before and after intensive exposure to docetaxel and identified potential ERBB2 target genes implicated in a variety of cellular processes including cell proliferation, cell adhesion, apoptosis and cytoskeleton organization. Comparison of the transcriptome of the cell lines before and after docetaxel exposure revealed substantially different expression patterns. Twenty-one differentially expressed genes between HB4a and C5.2 cell lines, before and after docetaxel treatment, were further analyzed by qPCR. The alterations in the expression patterns in HB4a and C5.2 cell lines in response to docetaxel treatment observed by SAGE analysis were confirmed by qPCR for the majority of the genes analyzed. Our study provides a comprehensive view of the expression changes induced in two human mammary cells expressing different levels of ERBB2 in response to docetaxel that could contribute to the elucidation of the mechanisms involved in ERBB2-mediated chemoresistance in breast cancer. (AU)

• Processo FAPESP: 02/01524-9 - Efeito do docetaxel na expressão gênica global de células de mama: identificação de genes associados à quimiossensibilidade e quimiorresistencia
• Beneficiário: Maria Aparecida Nagai
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/01026-0 - Análise funcional de genes potencialmente regulados pelo receptor de estrógeno e/ou pelo oncogene ERBB2: implicações no diagnóstico, prognóstico e tratamento do câncer de mama
• Beneficiário: Maria Aparecida Nagai
• Modalidade de apoio: Auxílio à Pesquisa - Temático