Expression of the glucocorticoid receptor and K-ras genes in urethan-induced mouse lung tumors and transformed cell lines.
Glucocorticoids influence cell proliferation and differentiation in the lung. We examined the expression of the glucocorticoid receptor (GR) gene in urethan-induced mouse lung tumors and transformed lung cell lines to determine whether any altered responsiveness to these steroids is involved in the neoplastic development of some lung tumors. We find that a GR mRNA of similar size and amount is expressed in both normal lung and urethan-induced lung tumors. The K-ras gene is activated in urethan-induced lung adenomas and transformed lung cell lines. Both alveolar and papillary lung adenomas express slightly elevated levels of K-ras mRNA and similar levels of H-ras mRNA, but variable levels of c-myc mRNA, GR and K-ras mRNAs are concurrently expressed in a cyclic manner during the proliferation of nontransformed C10 and transformed A5 lung cell lines. Treatment of the C10 cells with dexamethasone (Dex) results in the inhibition of cell proliferation and the down-regulation of both the GR and K-ras mRNA. Dex treatment also down-regulated GR mRNA levels in A5 and LM2 cells, but no inhibitory effect was observed on K-ras mRNA levels or cell proliferation. These results suggest that glucocorticoids can inhibit K-ras expression in nontransformed lung cells. Although transformed lung cells respond to the steroid by down-regulation of the GR, the presence of an activated K-ras allele may override the inhibitory effects of these hormones on cell proliferation.
Hanson
L A
LA
Department of Pharmacology, Toxicology, and Therapeutic, University of Kansas Medical Center, Kansas City 66103.
Nuzum
E O
EO
Jones
B C
BC
Malkinson
A M
AM
Beer
D G
DG
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002461:Cell Line, Transformed / Q000378:metabolism*; D015342:DNA Probes; D003907:Dexamethasone / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D011905:Genes, ras / Q000235:genetics*; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008805:Mice, Inbred A; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000302:isolation & purification; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000235:genetics*; D014520:Urethane
D015342:DNA Probes; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011965:Receptors, Glucocorticoid; D014520:Urethane; D003907:Dexamethasone