The prostate gland contains basal and luminal cells, both of which have been identified as "cells-of-origin" for prostate cancer in recent mouse studies. However, the question of whether and where stem cells were present in the human prostate has been largely a medical mystery and a constant debate until now.

The team completed a genome-wide analysis of human benign prostate basal and luminal cells using RNA sequencing and found that they expressed genes differently and that some basal cells represented self-renewing adult stem cells.

"Strikingly, we found that basal stem cells also expressed a large cohort of 'proneural' genes that are normally involved in regulating the nervous system development," said the author. "These proneural genes seem to play important functions in conferring stem cell-like properties upon some basal cells."

This finding is important because a subset of prostate cancers (less than 5 percent) are highly aggressive and do not respond to current anti-prostate cancer treatments such as endocrine therapy.

"Surprisingly, these hard-to-treat cancers also express a gene signature that overlaps with our normal basal stem cell gene expression profile, suggesting that basal stem cells may represent the cell-of-origin for these prostate cancers," said the author. "Of significance, the basal stem cell gene expression profile is also linked to endocrine therapy-resistant cancer which is lethal to virtually all advanced prostate cancer patients."

The team also found that basal stem cells are enriched in a genetic component that is partially regulated by MYC which offers hope that the deadliest of prostate cancers and therapy-resistant prostate cancers may have a new therapeutic option.

"Our studies establish that therapy that combines Pol-I and MYC inhibitors may be a potential new line of treatment for highly metastatic and endocrine therapy-resistant prostate cancer," said the author.

https://www.mdanderson.org/newsroom/2016/02/study-links-normal-s.html