Parathyroid hormone-related protein (PTHrP) plays a major role in breast and prostate carcinoma progression and bone metastasis. PTHrP has also been shown to be the primary factor responsible for humoral hypercalcemia of malignancy. Vitamin D₃ and its noncalcemic analogue EB1089 have been reported to inhibit growth of cells derived from a variety of tumours in vitro and in vivo. Using the breast cancer MCF7 and the prostate cancer PC3 cell lines as a model, we investigated the effects of different doses (10⁻⁷ M to 10⁻⁸ M) of these therapeutic agents on PTHrP mRNA expression during 24 h treatments. In both cell lines, PTHrP mRNA levels were low with EB1089 compared with those treated with Vitamin D₃. In addition, the EB1089 (10⁻⁸ M) was more effective in induction of the PTHrP mRNA in PC3 cells than in MCF7. We conclude our present results indicate that both Vitamin D₃ and EB1089 suppress PTHrP gene transcription in prostate cancer PC3 cell line and breast cancer MCF7 cell line and EB1089 was more effective than Vitamin D₃ on these cells.