Overexpression of the 32-kilodalton dopamine and cyclic adenosine 3',5'-monophosphate-regulated phosphoprotein in common adenocarcinomas.

Abstract

The 32-kilodalton dopamine and cyclic adenosine 3',5'-monophosphate-regulated phosphoprotein (DARPP-32) is the only known protein that can act as a protein phosphatase-1 inhibitor or a protein kinase inhibitor. It is known as a neurogenic protein that plays a major role in dopamine regulation in the central nervous system. Recently, DARPP-32 and a truncated isoform, t-DARPP, have been cloned in gastric carcinoma. The extent of DARPP-32 and t-DARPP expression in human epithelial tissues and carcinomas remained unknown. Using tissue microarrays and an antibody to DARPP-32, the authors evaluated the immunohistochemical findings in 43 different normal epithelium human tissue samples and in 187 samples of common carcinomas of breast, prostate, colon, and stomach. DARPP-32 proteins were expressed at varying levels in several types of normal epithelial tissues outside of the central nervous system. Using quantitative real-time reverse transcriptase-polymerase chain reaction analysis, the authors demonstrated that both DARPP-32 and t-DARPP mRNAs frequently were overexpressed in carcinomas of the breast, prostate, colon, and stomach compared with normal tissue samples. Immunohistochemical analysis of tissue microarrays that contained 187 carcinoma samples confirmed the strong expression of DARPP-32 proteins in these tumor types. The current study provides the first evidence that DARPP-32 expression is not limited to dopamine signaling in normal cells of the central nervous system. The pattern of expression of DARPP-32 proteins in normal epithelial tissues suggests that these proteins play an important role in epithelial signaling that may be tissue specific. Moreover, the observation that DARPP-32 and t-DARPP frequently are overexpressed in common subtypes of human adenocarcinomas suggest that these proteins may be important in tumorigenesis.