ACTIVATION OF PROTEIN KINASE-A INCREASES THE INVITRO INVASION, MIGRATION, AND ADHERENCE TO RECONSTITUTED BASEMENT-MEMBRANE BY LEWIS LUNG-CARCINOMA TUMOR-CELLS

Prostaglandin E2 (PGE2) stimulated in vitro invasion, migration, and a dherence to reconstituted basement membrane by metastatic Lewis lung c arcinoma (LLC) clones, but this stimulation was blocked by protein kin ase A (PKA) inhibitors and by expression of a transfected mutant R(Ial pha) which blocks PKA activation. In vitro migration and adherence of metastatic LLC transfectants was heightened by expression of a transfe cted C(alpha) gene and further heightened by Zn2+ induction of the exp ression vector. Nonmetastatic LLC were not migratory nor invasive. How ever, nonmetastatic LLC that were stably transfected with a C(alpha) g ene were both migratory and invasive, particularly when C(alpha) expre ssion was further induced with Zn2+. The results of these in vitro stu dies show that PKA can enhance the metastatic characteristics of LLC.