Altered dexamethasone responsiveness and loss of growth control in tumorigenic mouse lung cell lines.
Glucocorticoid hormones induce differentiation, inhibit proliferation, and, in mice, reduce carcinogen-induced tumorigenesis of lung epithelial cells. Therefore we examined dexamethasone effects on tumorigenic and non-tumorigenic mouse lung epithelial-derived cell lines. Non-tumorigenic cells were growth inhibited and exhibited CAT activity in pMMTV-CAT transfectants in response to dexamethasone. Tumorigenic cell lines exhibited a range of responses to dexamethasone. While one tumorigenic line was growth-inhibited and responsive in CAT assays, 2 other tumorigenic cell lines were unresponsive both in CAT and in growth assays. A fourth tumorigenic cell line exhibited intermediate sensitivity in CAT assays and was actually growth-enhanced by dexamethasone. Although no difference between cell lines was observed in the abundance of glucocorticoid receptor protein on Western blots, the least dexamethasone-responsive tumorigenic lines exhibited very little binding of 3H-dexamethasone. Clones of tumorigenic lines stably transfected with the rat glucocorticoid receptor gene were more dexamethasone-sensitive in CAT assays and were growth-inhibited by dexamethasone. These data suggest that the neoplastic progression of cell lines derived from mouse lung frequently involves the acquisition of diminished glucocorticoid responsiveness.
Droms
K A
KA
Environmental and Occupational Health Center, University of Kansas Medical Center, Kansas City 66103.
Hanson
L A
LA
Malkinson
A M
AM
Beer
D G
DG
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology*; D015870:Gene Expression / Q000235:genetics; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D051379:Mice; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000502:physiology; D012680:Sensitivity and Specificity; D014162:Transfection; D014316:Tritium; D014407:Tumor Cells, Cultured
D011965:Receptors, Glucocorticoid; D014316:Tritium; D003907:Dexamethasone