Regulation of protein kinase a activation and prostaglandin E2-stimulated migration of lewis lung carcinoma clones

✍ Scribed by M. Rita Young I.; Melvin E. Young; Yvonne Lozano; Michael Coogan; Jamila M. Bagash

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: French
• Weight: 761 KB
• Volume: 49
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910490127

✦ Synopsis

Lewis lung carcinoma (LLC) clones were used in in vitro models for dissemination to identify mechanisms regulating the stimulation of metastatic LLC-LN7 migration by prostaglandin E , (PGE,) o r forskolin plus 3-isobutyl-I -methylxanthine (IBMX), and the lack of responsiveness t o generated cAMP in non-metastatic LLC-C8 cells. The regulatory subunits of protein kinase A (PKA) from LLC-LN7 cells bound more 8-N,-32P-cAMP, even though production of regulatory subunits was equal to that in LLC-CE cells. Protein kinase C (PKC) differentially regulated PKA activation in the LLC variants. PKC activation inhibited PGE,-stimulated migration by LLC-LN7 cells. Inhibition of PKC with staurosporine stimulated LLC-LN7 cell migration to a level comparable with that induced by PGE,. However, PGE, did not further stimulate the migration of staurosporine-treated cells. The PGE, or staurosporine stimulation of LLC-LN7 cell migration was dependent on PKA activation. The effects that modulation of PKA and PKC had on LLC-LN7 cell migration paralleled the effects on endogenous protein phosphorylation. LLC-LN7 cell autophosphorylation was stimulated to a similar degree by PGE, , forskolin plus IBMX, staurosporine, or the combination of staurosporine and forskolin plus IBMX. In contrast, neither migration nor autophosphorylation was stimulated in nonmetastatic LLC-C8 cells by cAMP elevation or by PKC inhibition. Autophosphorylation, although not migration, of LLC-C8 cells was stimulated by forskolin plus IBMX when PKC activity was inhibited. These results suggest that the increased PKA response of metastatic LLC-LN7 cells is contributed by an increased binding of cAMP by the PKA regulatory subunits and a reduced level of regulation by PKC.