Identification of prostate cancer genes opens door to new treatments

22 May 2008

For the first time researchers have identified the genetic profile of prostate cancer stem cells. The study by the YCR Cancer Research Unit at the University of York, England, and Pro-cure Therapeutics Ltd, could lead to new ways for treating the cancer.

The findings, published in Genome Biology [1], revealed 581 genes that are differentially expressed in certain prostate cancer cells, highlighting several pathways important in the cancer stem-cell biology, and offering targets for new chemopreventative and chemotherapeutic approaches.

“For the first time we are looking at the subpopulation of cancer cells which actually initiate new tumours” explains Anne Collins, who co-ordinated the study. “The genetic profiling we have carried out should stimulate new lines of research directed towards stem cell treatments for cancer."

The cells in the study represent less than 0.1% of prostate cancer tumours, and have properties that mark them out as cancer stem cells. The cells renew themselves, are highly invasive, and have a longer lifetime than normal stem cells. They also feature a primitive epithelial phenotype and can differentiate to recapitulate phenotypes seen in prostate tumours. The cells are found in all stages and types of prostate cancer.

Expression profiling of prostate cancers typically uses tumour cell mass samples to identify individual genes. In this study, researchers harnessed advances in microarray and target labelling technologies to produce a functionally annotated expression profile of these prostate cancer stem cells.

The research team created a malignant stem cell signature by combining genes significantly overexpressed in stem cells with those significantly overexpressed in malignant stem cells. Quantitative RT-PCR, flow cytometry and immunocytochemistry were used to validate the gene expression changes.

Genes associated with inflammation were prominent in the cancer stem cell expression profile. Potential therapeutic target NFκB is known to promote cell survival. The researchers showed that an NFκB inhibitor triggered programmed cell death in cancer stem cells, but spared normal stem cells. This provides a potential therapeutic target for this rare group of cells, which are unlikely to be affected by current chemotherapy regimens.


1. Birnie R, Bryce SD, Roome C, et al. Gene expression profiling of human prostate cancer stem cells reveals a pro-inflammatory phenotype and the importance of extracellular matrix interactions. Genome Biology, 20 May 2008. 9:R83doi:10.1186/gb-2008-9-5-r83.

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