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Unlike the bulk of cells in a tissue, stem cells are long-lived and capable of self-renewal. Enhanced life span and proliferative potential must be reflected in the cells’ gene expression program, such that gene products involved in self-renewal and antiapoptotic pathways will be exclusive to, or up-regulated in, the stem/progenitor cell fraction. Due to the common mechanisms underlying stem cell function, stem cells from different tissues are also expected to share markers to some extent.

Bcl-2 is an antiapoptotic protein which is expressed primarily in long-lived cells. Expression of bcl-2 can also be detected in the basal epithelial compart­ment in the prostate. Salm et al. suggested that high levels of bcl-2 expression in stem cells, in the proximal region of mouse prostatic ducts, prevent the cells from undergoing apoptosis due to high levels of TGF-(3 signaling, which main­tains stem cell quiescence. Association of bcl-2 expression with the stem cell compartment in prostate, however, remains to be demonstrated.

Telomerase is a ribonucleoprotein enzyme that prevents progressive shorten­ing of telomeres upon cell division, thus preventing chromosome end fusion and ultimately cell death. It is therefore expressed in various cancers where sustained self-renewal capacity of cells is required, whereas expression is absent from adult somatic cells. Telomerase is expressed throughout the basal compartment in adult human prostate. Whether it is expressed in the stem cell fraction, how­ever, has yet to be elucidated. Owing to the infrequent cycling of stem cells, telomerase expression in this cell fraction might not be required. Supporting this assumption, Jaras et al. demonstrated that an increase in hTERT expression in murine hematopoietic stem cells was concomitant with decreased self-renewal capacity.

Notch signaling has a role in the maintenance of hematopoietic stem cells. Shou et al. mapped the Notch 1 receptor to basal epithelial cells in the murine prostate using a transgenic mouse model that expressed enhanced green fluores­cent protein (eGFP) under the control of the Notchl promoter. To further assess the role of Notch on prostate development, Wang et al. generated a transgenic mouse model expressing the prodrug-converting enzyme nitroreductase, under the control of the Notchl promoter, which allows controlled elimination of Notchl expressing cells by administration of nitroreductase substrate. Ablation of Notchl-expressing cells severely affected morphogenesis, growth, and differentiation in murine prostate, suggesting that it is expressed in the stem cell compartment.

A further marker of basal epithelial cells in the prostate is p63, a homolog of tumor suppressor p53, which acts on the expression of a wide spectrum of target genes via multiple protein isoforms. Mice bearing a germline inacti-vation of p63 fail to develop a prostate gland, which suggests that the frac­tion of p63-expressing cells in the prostate comprises the stem cells. Another gene selectively expressed in basal prostate epithelium is pp32, which codes for a nuclear phosphoprotein and has been identified in anatomically defined stem cell compartments of normal human tissues such as intestinal crypt epithelial cells. Whether pp32 expression is restricted to the stem cell compartment in prostate has yet to be elucidated.

As stated previously, prostate epithelial stem cells express high levels of integrin oi2Pi and CD133, the latter being expressed exclusively in the stem cell fraction of the human prostate. A putative prostate stem cell frac­tion has also been isolated on the basis of a side population phenotype. On a molecular level, this phenotype is determined by the pres­ence of membrane efflux pumps of the ATP-binding cassette (ABC) transporter superfamily. Prostate stem cell antigen (PSCA), a homolog to thymocyte stem cell antigen 2, maps to a subset of basal cells in sections of benign prostate. Rather than identifying it as a prostate stem cell marker, however, studies in a trans-genic mouse model identified PSCA as a marker of transit-amplifying cells. Markers shown to typify other types of stem cells include Oct4, nanog (embryonic stem cells), and P-catenin (intestinal stem cells) as well as nestin (neu­ral stem cells). Whether these markers are expressed in prostate epithelial stem cells has yet to be determined.