INTEGRITY OF THE 1,25-DIHYDROXYVITAMIN D-3 RECEPTOR IN BONE, LUNG, AND OTHER CANCERS

Differentiation and proliferation can be regulated in diverse cell typ es by 1,25-dihydroxyvitamin D-3 These effects derive from modulation o f gene expression mediated by the interaction of 1,25-dihydroxyvitamin D, with the vitamin D receptor (VDR). The VDR is one of the nuclear h ormone receptors. Because these transcription factors play a key role in growth control, some nuclear hormone receptors, such as the retinoi c acid receptor a, can be disrupted in cancer. With these alterations in mind, we looked for alterations of the VDR gene in a variety of can cers, including 68 osteosarcomas, 23 other sarcomas, 34 non-small cell lung cancers, and 44 cell lines representing many tumor types. Cross integrity of the VDR gene was examined on Southern blots probed with t he coding region of the VDR cDNA. The presence of point mutations targ eting VDR exons 2-7 was assessed by polymerase chain reaction-single-s trand conformation polymorphism analysis and direct DNA sequencing. Tw o alterations were detected; direct DNA sequencing of these samples re vealed one silent mutation in codon 79 and a base change in intron 3. These results suggest that mutations and rearrangement of the VDR do n ot play a role in the cancers studied. (C) 1997 Wiley-Liss, Inc.