Regucalcin was identified as a calcium (Ca2+)-binding protein playing an important role in maintenance of intracellular Ca2+ homeostasis. More recently, proteomic studies have identified it as a down-regulated gene in mouse and human hepatocellular carcinomas. In addition, regucalcin effects in kidney and liver cells, suppressing cell proliferation, inhibiting expression of oncogenes, and increasing the expression of tumor suppressor genes, have been described.
Prostate cancer depends on the trophic effects of androgens, and altered Ca2+ homeostasis and signaling have been associated with the development of this pathology. Therefore, in the present study we analyzed regucalcin expression, in neoplasic and non-neoplasic prostate tissue and cells, by means of RT-PCR, western blot and immunohistochemistry. Regucalcin localizes in cell nuclei and cytoplasm and its expression was diminished in prostate cancer cases. Moreover, regucalcin immunoreactivity was negatively associated with cellular differentiation of prostate adenocarcinoma. The effect of the non-aromatizable androgen 5-alpha-dihydrotestosterone (DHT) on regucalcin expression in vitro, in LNCaP prostate cancer cells, and in vivo, in a rat animal model, was determined. Real-time PCR analysis showed that DHT downregulates regucalcin expression, an effect inhibited in the presence of both flutamide and cyclohexamide, suggesting the involvement of androgen receptor and de novo protein synthesis.
The loss of regucalcin expression in prostate cancer cases and the regulation of its expression by androgens suggest that it may be associated with tumor development and/or progression.