Regucalcin plays an important role in maintenance of intracellular Ca(2+) homeostasis, suppresses cell proliferation, inhibits expression of oncogenes, and increases the expression of tumour suppressor genes. This suggests that regucalcin functions may be altered in cancer tissues. In this study the regucalcin expression in breast and prostate cancer cases was analysed by RT-PCR and immunohistochemistry showing that the mRNA and/or protein are under-expressed in these tumors. The effect of sex steroid hormones on regucalcin expression in breast and prostate cancer cells was determined by real-time PCR. MCF-7 and LNCaP cells were stimulated with 0, 1, and 10 nM of 17beta-estradiol (E(2)) or 5alpha-dihydrotestosterone (DHT), respectively, for 0, 6, 12, 24, and 48 h. MCF-7 cells were also stimulated with E(2) conjugated to BSA (E(2)-BSA). To explore the mechanisms underlying the sex steroid regulation of regucalcin expression, control treatments with ICI 182,780, flutamide and cyclohexamide were carried out. E(2) effects regulating regucalcin expression were not abrogated in the presence of ICI 182,780, and were similar to those observed with E(2)-BSA, which suggests the involvement of a membrane-bound estrogen receptor. In LNCaP cells, DHT down-regulated regucalcin expression, an effect inhibited by the presence of both flutamide and cyclohexamide, suggesting the involvement of androgen receptor and de novo protein synthesis. The loss of regucalcin expression in breast and prostate cancer cases and the regulation of its expression by sex steroid hormones suggest that it may be associated with development and progression of these human tumors.