CORTICOTROPIN-RELEASING FACTOR STIMULATES CYCLIC-AMP, ARACHIDONIC-ACID RELEASE, AND GROWTH OF LUNG-CANCER CELLS

The effects of corticotropin-releasing factor (CRF) on human lung canc er cell lines was investigated. Corticotropin-releasing factor increas ed the cAMP levels in a dose-dependent manner; CRF (100 nM) elevated t he cAMP levels approximately elevenfold using NCI-H345 cells and incre ased the gastrin-releasing peptide (GRP) secretion rate by approximate ly 70%. Similarly, sauvagine, a structural analogue of CRF, elevated t he cAMP levels with a half-maximal effective dose (ED50) of 20 nM. The increase in cAMP caused by CRF and sauvagine was reversed by alpha-he lical CRF(9-41). Corticotropin-releasing factor had no effect on cytos olic calcium but stimulated [H-3]arachidonic acid release from NCI-H12 99 cells with an ED50 of 30 nM. The increase in [H-3]arachidonic acid release caused by 100 nM CRF was significantly reversed by 1 or 10 muM alpha-helical CRF(9-41). Also, CRF stimulated the clonal growth of NC I-H345 and H720 cells and the growth increase caused by CRF was revers ed by alpha-helical CRF(9-41). These data suggest that CRF may be a re gulatory peptide in lung cancer.