BACKGROUND: Anti-androgens are administered as a principal treatment for prostate cancer. Aggressive hormone refractory disease is characterized in some cases by the development of a neuroendocrine phenotype. However little attention has been paid to resistance pathways selected for by long-term treatment with non-steroidal anti-androgens.
METHODS: Using a resistant sub-line, LNCaP-Bic, we performed a comparative gene expression profiling using cDNA microarrays and target validation by qRT-PCR. Targets were then explored using cell proliferation, cell cycle analysis and in vitro invasion assays using siRNA technology.
RESULTS: Neurotensin/Neuromedin N (NTS) was upregulated in the LNCaP-Bic line at both the transcript and protein level. The resistant line was found to have an increased proliferation rate, more rapid cell cycle progression and increased invasiveness through Matrigel. Each phenotypic difference could be reduced using siRNA knockdown of NT.
CONCLUSION: Increased expression of NT in bicalutamide resistant prostate cancer cells induces cell proliferation and invasion suggesting that this peptide may contribute to the development of bicalutamide resistant prostate cancer.
Bibliographical note(c) 2006 Wiley-Liss, Inc.
- Androgen Antagonists
- Cell Cycle
- Cell Line, Tumor
- Cell Movement
- Cell Proliferation
- Drug Resistance, Neoplasm
- Gene Expression Profiling
- Microsatellite Repeats
- Oligonucleotide Array Sequence Analysis
- Prostatic Neoplasms
- RNA, Small Interfering
- Reverse Transcriptase Polymerase Chain Reaction
- Tosyl Compounds