MCF-7/VDR: A new vitamin D resistant cell line

Several in vitro and in vivo experiments have demonstrated potent cell regu latory effects of vitamin D compounds in cancer cells. Moreover, a promisin g phase 1 study with the vitamin D analogue Seocalcitol (EB 1089) in patien ts with advanced breast and colon cancer has already been carried out and m ore clinical trials evaluating the clinical effectiveness of EB 1089 in oth er cancer types are in progress (Mork Hansen et al. [2000a]). However, only little is known about the mechanisms underlying the actions of vitamin D o r about the possible development of drug resistance in the patients. Theref ore, in an attempt to gain more insight into these aspects, we have develop ed the MCF-7/VDR cell fine, a stable subclone of the human MCF-7 breast can cer cell fine, which is resistant to the growth inhibitory and apoptosis in ducing effects of 1 alpha ,25(OH)(2)D-3. Despite this characteristic, recep tor studies on the VDR have clearly demonstrated that the MCF-7/VDR cells c ontain fully functional VDRs, although in a lower number than seen with the parental MCF-7 cells. The regulation of the 24-hydroxylase enzyme appeared to be intact in the MCF-7/VDR cells and no differences with regard to grow th rate and morphological appearance between the MCF-7/VDR cells and the pa rental MCF-7 cells were observed. interestingly, however, the sensitivity o f the MCF-7/VDR cells to the pure anti-estrogen ICI 182,780 was found to be increased. The MCF-7/VDR cell line shows characteristics different from th ose of previously described vitamin D resistant breast cancer cell lines bu t also some similarities. Together such vitamin D resistant cell lines ther efore serve as a useful tool for studying the exact mechanism of action of vitamin D and the development of vitamin D resistance. (C) 2001 Wiley-Liss, Inc.