High frequency of retinoic acid receptor beta abnormalities in human lung cancer.
One of the three human retinoic acid receptors, RAR-beta, maps to a region on the short arm of chromosome 3 frequently deleted in lung cancer. Because retinoic acid is required for normal epithelial cell growth and regulation, and loss of a retinoic acid receptor might be expected to contribute to oncogenesis, we examined RAR-beta RNA and DNA in normal lung, 33 lung cancer cell lines and nine primary lung tumors. Normally, RAR-beta is expressed as two transcripts, of sizes 3.1 kb and 2.8 kb, which are strongly induced by retinoic acid. At least 50% of the cell lines and 30% of the tumor samples show altered RAR-beta expression and/or inducibility, including examples of absence or specific loss of one of the RAR-beta transcripts. Abnormalities in the expression patterns of RAR-alpha and RAR-gamma also are found, but at a lower frequency than RAR-beta abnormalities. Southern analysis reveals alteration of the RAR-beta gene in three of the cell lines. Our data suggest that abnormalities in structure and expression of the RAR-beta gene may be involved in the pathogenesis of lung cancer.
Gebert
J F
JF
Molecular Medicine Unit, Beth Israel Hospital, Boston, Massachusetts 02215.
Moghal
N
N
Frangioni
J V
JV
Sugarbaker
D J
DJ
Neel
B G
BG
D002352:Carrier Proteins / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000737:chemistry / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D012313:RNA / Q000032:analysis; D012334:RNA, Neoplasm / Q000378:metabolism; D018168:Receptors, Retinoic Acid; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D012313:RNA