Steroid hormones are thought to act as inducers, promoters or permissive factors in the carcinogenesis of hormone sensitive tissues in experimental animals and in humans. Hormone sensitivity of normal and neoplastic tissues is to a significant degree related to hormone receptor concentrations. This observation has been found clinically useful in the treatment selection for cancer patients with hormonally responsive tumors. The significance of the present study is that it should provide evidence for the importance or lack of importance of 1,25(OH)2D3 as a regulatory factor for growth of certain cancers. Moreover, the finding that the cell types that respond to 1,25(OH)2D3 are distinct from cells that are responsive to sex steroids or glucocorticoids may result in increasing the number of tumor types that are amenable to hormone therapy. The specific objective of this study is to provide evidence to support a role for the hormone 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) in the maintenance and proliferation of malignant cells. For this study we will examine established malignant cell lines derived from tumors arising in 1,25(OH)2D3 responsive tissues and correlate the concentration of receptors for 1,25(OH)2D3 with cell proliferation and calcium metabolism. This investigation will provide information that will be useful in determining the potential clinical significance of 1,25(OH)2D3 and its analogs in modulating tumor cell proliferation. Furthermore, it will help illucidate whether determination of 1,25(OH)2D3 receptor levels can be used as an indicator of tumor cell responsiveness in much the same way as estrogen receptor levels are now used to detect hormonally responsive breast carcinomas. This study will also identify cell culture systems that are responsive to 1,25(OH)2D3 and that may prove useful for the analysis of the mechanism of action of this hormone.
Showing the most recent 10 out of 13 publications
