Integrity of the 1,25-dihydroxyvitamin D3 receptor in bone, lung, and other cancers

✍ Scribed by Carl W. Miller; Roberta Morosetti; Moray J. Campbell; Susana Mendoza; H. Phillip Koeffler

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 102 KB
• Volume: 19
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/(sici)1098-2744(199708)19:4<254::aid-mc6>3.0.co;2-c

✦ Synopsis

Differentiation and proliferation can be regulated in diverse cell types by 1,25-dihydroxyvitamin D 3 . These effects derive from modulation of gene expression mediated by the interaction of 1,25-dihydroxyvitamin D 3 with the vitamin D receptor (VDR). The VDR is one of the nuclear hormone receptors. Because these transcription factors play a key role in growth control, some nuclear hormone receptors, such as the retinoic acid receptor α, can be disrupted in cancer. With these alterations in mind, we looked for alterations of the VDR gene in a variety of cancers, including 68 osteosarcomas, 23 other sarcomas, 34 non-small cell lung cancers, and 44 cell lines representing many tumor types. Gross integrity of the VDR gene was examined on Southern blots probed with the coding region of the VDR cDNA. The presence of point mutations targeting VDR exons 2-7 was assessed by polymerase chain reaction-single-strand conformation polymorphism analysis and direct DNA sequencing. Two alterations were detected; direct DNA sequencing of these samples revealed one silent mutation in codon 79 and a base change in intron 3. These results suggest that mutations and rearrangement of the VDR do not play a role in the cancers studied.