Regulation of microtubule, apoptosis, and cell cycle-related genes by taxotere in prostate cancer cells analyzed by microarray

Neoplasia. Mar-Apr 2004;6(2):158-67. doi: 10.1593/neo.03391.

Abstract

Taxotere showed antitumor activity against solid tumors including prostate cancer. However, the molecular mechanism(s) of action of Taxotere has not been fully elucidated. In order to establish such molecular mechanism(s) in both hormone-insensitive (PC3) and hormone-sensitive (LNCaP) prostate cancer cells, comprehensive gene expression profiles were obtained by Affymetrix Human Genome U133A Array. The RNA from the cells treated with 2 nM Taxotere was subjected to microarray analysis. We found that a total of 166, 365, and 1785 genes showed greater than two-fold change in PC3 cells after 6, 36, and 72 hours of treatment, respectively compared to 57, 823, and 964 genes in LNCaP cells. The expression of tubulin was decreased, whereas the expression of microtubule-associated proteins was increased in Taxotere-treated prostate cancer cells, confirming the microtubule-targeting effect of Taxotere. Clustering analysis showed downregulation of some genes for cell proliferation and cell cycle. In contrast, Taxotere upregulated some genes that are related to induction of apoptosis and cell cycle arrest. From these results, we conclude that Taxotere caused alterations of a large number of genes, many of which may contribute to the molecular mechanism(s) by which Taxotere affects prostate cancer cells. Further molecular studies are needed in order to determine the cause and effect relationships between these genes altered by Taxotere. Nevertheless, our results could be further exploited for devising strategies to optimize therapeutic effects of Taxotere for the treatment of prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / genetics*
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Cell Cycle Proteins / genetics*
  • Docetaxel
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Male
  • Microtubule Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Taxoids / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Microtubule Proteins
  • Taxoids
  • Docetaxel