Androgen repression of cytokeratin gene expression during rat prostate differentiation: evidence for an epithelial stem cell-associated marker.

Cytokeratin (CK) 8 mRNA expression in developing and degenerating rat prostate was studied using in situ hybridization with an antisense RNA-probe. It was found that: 1) the CK 8 antisense probe was accumulated only within prostatic epithelial cells; 2) after castration, CK 8 mRNA signals in ventral prostate (VP) sections were significantly increased, and elevated CK 8 mRNA expression persisted even long after prostate involution was complete; and 3) during prostate development, the strongest CK 8 mRNA staining was found in the early neonatal prostatic epithelia which were composed mainly of prostatic stem cells. Thereafter, a shift of CK 8 mRNA staining to peripheral regions and decreased overall CK 8 mRNA levels were noted. These data indicate that excessive expression of CK 8 mRNA is a characteristic of prostatic stem cells, and CK molecules are excellent markers for determining the hierarchical pathway of cell differentiation in prostate epithelium.