LNCaP Atlas: Gene expression associated with in vivo progression to castration-recurrent prostate cancer

Abstract

Background

There is no cure for castration-recurrent prostate cancer (CRPC) and the mechanisms underlying this stage of the disease are unknown.

Methods

We analyzed the transcriptome of human LNCaP prostate cancer cells as they progress to CRPC in vivo using replicate LongSAGE libraries. We refer to these libraries as the LNCaP atlas and compared these gene expression profiles with current suggested models of CRPC.

Results

Three million tags were sequenced using in vivo samples at various stages of hormonal progression to reveal 96 novel genes differentially expressed in CRPC. Thirty-one genes encode proteins that are either secreted or are located at the plasma membrane, 21 genes changed levels of expression in response to androgen, and 8 genes have enriched expression in the prostate. Expression of 26, 6, 12, and 15 genes have previously been linked to prostate cancer, Gleason grade, progression, and metastasis, respectively. Expression profiles of genes in CRPC support a role for the transcriptional activity of the androgen receptor ( CCNH, CUEDC2, FLNA, PSMA7), steroid synthesis and metabolism ( DHCR24, DHRS7, ELOVL5, HSD17B4, OPRK1), neuroendocrine ( ENO2, MAOA, OPRK1, S100A10, TRPM8), and proliferation ( GAS5, GNB2L1, MT-ND3, NKX3-1, PCGEM1, PTGFR, STEAP1, TMEM30A), but neither supported nor discounted a role for cell survival genes.

Conclusions

The in vivo gene expression atlas for LNCaP was sequenced and support a role for the androgen receptor in CRPC.