AbstractHousekeeping (HK) genes are involved in basic cellular functions and tend to be constitutively expressed across various tissues and conditions. A number of studies have analyzed the value of HK genes as an internal standard for assessing gene expression, but the role of HK genes in cancer development has never been specifically addressed. In this study, we sought to evaluate the expression of HK genes during prostate tumorigenesis. We performed a meta‐analysis of gene expression during the transition from normal prostate (NP) to localized prostate cancer (LPC) (i.e., NP > LPC) and from localized to metastatic prostate cancer (MPC) (i.e., LPC > MPC). We found that HK genes are more likely to be differentially expressed during prostate tumorigenesis than is the average gene in the human genome, suggesting that prostate tumorigenesis is driven by modulation of the expression of HK genes. Cell‐cycle genes and proliferation markers were up‐regulated in both NP > LPC and LPC > MPC transitions. We also found that the genes encoding ribosomal proteins were up‐regulated in the NP > LPC and down‐regulated in the LPC > MPC transition. The expression of heat shock proteins was up‐regulated during the LPC > MPC transition, suggesting that in its advanced stages, prostate tumor is under cellular stress. The results of these analyses suggest that during prostate tumorigenesis, there is a period when the tumor is under cellular stress and, therefore, may be the most vulnerable and responsive to treatment. © 2009 UICC