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 turnorigenic lines stably transfected with the rat glucocorticoid receptor gene were more dexarnethasone‐sensitive in CAT assays and were growthinhibited by dexamethasone. These data suggest that the neoplastic progression of cell lines derived from mouse lung frequently involves the acquisition of diminished glucocorticoid responsiveness.

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