{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T17:39:02Z","timestamp":1760981942731},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,7,18]],"date-time":"2006-07-18T00:00:00Z","timestamp":1153180800000},"content-version":"vor","delay-in-days":5447,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[1991,8,19]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lewis lung carcinoma (LLC) clones were used in <jats:italic>in vitro<\/jats:italic> models for dissemination to identify mechanisms regulating the stimulation of metastatic LLC\u2010LN7 migration by prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>) or forskolin plus 3\u2010isobutyl\u2010I\u2010methyl\u2010xanthine (IBMX), and the lack of responsiveness to generated cAMP in non\u2010metastatic LLC\u2010C8 cells. The regulatory subunits of protein kinase A (PKA) from LLC\u2010LN7 cells bound more 8\u2010N<jats:sub>3<\/jats:sub>\u2010<jats:sup>32<\/jats:sup>P\u2010cAMP, even though production of regulatory subunits was equal to that in LLC\u2010C8 cells. Protein kinase C (PKC) differentially regulated PKA activation in the LLC variants. PKC activation inhibited PGE<jats:sub>2<\/jats:sub>\u2010stimulated migration by LLC\u2010LN7 cells. Inhibition of PKC with staurosporine stimulated LLC\u2010LN7 cell migration to a level comparable with that induced by PGE<jats:sub>2<\/jats:sub>. However, PGE<jats:sub>2<\/jats:sub> did not further stimulate the migration of staurosporine\u2010treated cells. The PGE<jats:sub>2<\/jats:sub> or staurosporine stimulation of LLC\u2010LN7 cell migration was dependent on PKA activation. The effects that modulation of PKA and PKC had on LLC\u2010LN7 cell migration paralleled the effects on endogenous protein phosphorylation. LLC\u2010LN7 cell autophosphorylation was stimulated to a similar degree by PGE<jats:sub>2<\/jats:sub>, forskolin plus IBMX, staurosporine, or the combination of staurosporine and forskolin plus IBMX. In contrast, neither migration nor autophosphorylation was stimulated in nonmetastatic LLC\u2010C8 cells by cAMP elevation or by PKC inhibition. Autophosphorylation, although not migration, of LLC\u2010C8 cells was stimulated by forskolin plus IBMX when PKC activity was inhibited. These results suggest that the increased PKA response of metastatic LLC\u2010LN7 cells is contributed by an increased binding of cAMP by the PKA regulatory subunits and a reduced level of regulation by PKC.<\/jats:p>","DOI":"10.1002\/ijc.2910490127","type":"journal-article","created":{"date-parts":[[2007,2,19]],"date-time":"2007-02-19T22:19:42Z","timestamp":1171923582000},"page":"150-155","source":"Crossref","is-referenced-by-count":20,"title":["Regulation of protein kinase a activation and prostaglandin E<sub>2<\/sub>\u2010stimulated migration of lewis lung carcinoma clones"],"prefix":"10.1002","volume":"49","author":[{"suffix":"I.","given":"M. 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