The PSCA gene was originally identified by Reiter el al. (1998) through an analysis of genes up-regulated in the human prostate cancer LAPC-4 xenograft model. The PSCA gene is located on chromosome 8q24.2.

In normal human tissues, PSCA mRNA expression is found in the prostate, with lower expression in placenta and very low expression in kidney and small intestine (Reiter et al., 1998; Cunha et al., 2006). Within normal human prostate sections, in situ hybridizations by Reiter el al. (1998) demonstrated PSCA mRNA expression in the subjacent basal cells, while Ross et al. (2002) demonstrated PSCA mRNA expression in the secretory luminal cells. These contrasting results may be due to sampling error from relatively small biopsies, since PSCA protein expression was seen in both cell types (see below).

The PSCA gene encodes a 123 amino acid cell surface protein with a molecular weight of 10-24 kDa (Reiter et al., 1998). Inaccurately named for its 30% homology to stem cell antigen type 2 (SCA-2), an immature lymphocyte cell surface marker, PSCA is neither a marker for a stem cell population nor is it exclusively expressed in the prostate. Like SCA-2 however, PSCA is a member of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI) anchored surface proteins.

In the human prostate, PSCA protein expression is found in both the basal and secretory epithelial cell layers, along with the neuroendocrine cells. Additionally, PSCA protein expression was demonstrated in the placenta, the bladder, the neuroendocrine cells of the stomach and colon, and weakly in the kidneys excluding the glomeruli (Gu et al., 2000).

PSCA is localized to the cell surface, anchored by a GPI linkage.

Although the function of PSCA is currently unknown, PSCA homologues give some insight into possible functions. It has been previously shown that proteins in the Thy-1 family have been reported to function in T cell activation (Presky et al., 1990) and proliferation, stem cell survival, and cytokine and growth factor response (Rege et al., 2006), while the family of Ly-6 genes has been associated with carcinogenesis (Treister et al., 1998; Witz et al., 2000), cellular activation (Malek et al., 1986) and cell adhesion of tumor cells (Eshel et al., 2000). PSCA does not seem to be critical for normal development or urogenital function since a PSCA knockout mouse created by Moore et al. (2008) was viable, grew to adulthood and had normal litters. Additionally, these PSCA knockout mice did not have an increased incidence of carcinogenesis.

A murine PSCA (mPSCA) homologue was also identified by Reiter et al. (1998) and it is located on chromosome 15. mPSCA has 70% homology to human PSCA at the nucleotide and amino acid levels.

While no mutation is known for PSCA, a recent study by the Study Group of Millennium Genome Project for Cancer (2008) found a significant association between two Single Nucleotide Polymorphisms (SNPs) in the PSCA gene and diffuse-type gastric cancer.