Integrity of the 1,25-dihydroxyvitamin D3 receptor in bone, lung, and other cancers. 1997

C W Miller, and R Morosetti, and M J Campbell, and S Mendoza, and H P Koeffler
Division of Hematology/Oncology, Cedars-Sinai Research Institute, University of California at Los Angeles School of Medicine 90048, USA.

Differentiation and proliferation can be regulated in diverse cell types by 1,25-dihydroxyvitamin D3. These effects derive from modulation of gene expression mediated by the interaction of 1,25-dihydroxyvitamin D3 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 alpha, 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.

UI MeSH Term Description Entries
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D001859 Bone Neoplasms Tumors or cancer located in bone tissue or specific BONES. Bone Cancer,Cancer of Bone,Cancer of the Bone,Neoplasms, Bone,Bone Neoplasm,Neoplasm, Bone
D002289 Carcinoma, Non-Small-Cell Lung A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy. Carcinoma, Non-Small Cell Lung,Non-Small Cell Lung Cancer,Non-Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinoma,Nonsmall Cell Lung Cancer,Carcinoma, Non Small Cell Lung,Carcinomas, Non-Small-Cell Lung,Lung Carcinoma, Non-Small-Cell,Lung Carcinomas, Non-Small-Cell,Non Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinomas
D005091 Exons The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA. Mini-Exon,Exon,Mini Exon,Mini-Exons
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012509 Sarcoma A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. Sarcoma, Epithelioid,Sarcoma, Soft Tissue,Sarcoma, Spindle Cell,Epithelioid Sarcoma,Epithelioid Sarcomas,Sarcomas,Sarcomas, Epithelioid,Sarcomas, Soft Tissue,Sarcomas, Spindle Cell,Soft Tissue Sarcoma,Soft Tissue Sarcomas,Spindle Cell Sarcoma,Spindle Cell Sarcomas
D012516 Osteosarcoma A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed) Sarcoma, Osteogenic,Osteogenic Sarcoma,Osteosarcoma Tumor,Osteogenic Sarcomas,Osteosarcoma Tumors,Osteosarcomas,Sarcomas, Osteogenic,Tumor, Osteosarcoma,Tumors, Osteosarcoma
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015139 Blotting, Southern A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES. Southern Blotting,Blot, Southern,Southern Blot
D016133 Polymerase Chain Reaction In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. Anchored PCR,Inverse PCR,Nested PCR,PCR,Anchored Polymerase Chain Reaction,Inverse Polymerase Chain Reaction,Nested Polymerase Chain Reaction,PCR, Anchored,PCR, Inverse,PCR, Nested,Polymerase Chain Reactions,Reaction, Polymerase Chain,Reactions, Polymerase Chain

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