Signal transduction cascade shared by epidermal growth factor and platelet-derived growth factor is a major pathway for oncogenic transformation in NRK cells .

Masuda A ; Kizaka-Kondoh S ; Miwatani H ; Terada Y ; Nojima H ; Okayama H

Laboratory of Ultrastructure Research , Aichi Cancer Center Research Institute , Nagoya , Japan .

New Biol 4 : 489-503 ( 1992)

Abstract
We have isolated two recessive , mutually complementary NRK cell mutants that are refractory to transformation by epidermal growth factor ( EGF ) and transforming growth factor-beta . Both mutants are defective in a signal transduction cascade shared by EGF and platelet-derived growth factor ( PDGF ) . Analysis of the mutants suggests that transformation of NRK cells by the v-fms , v-erbB , activated erbB-2 , v-ras , v-fos , v-mos , v-fes , v-src , SV40 large T , polyomavirus middle T , and human papillomavirus type 16 E6,E7 oncogenes is mediated by the EGF/PDGF signal cascade . The data also suggest that the EGF/PDGF cascade branches into mitogenic and oncogenic signals , the latter of which is required for soft agar growth and focus formation .

Gene Symbols

Chemical Identifiers ( Names)

Increase of migration of cultured endothelial cells by angiotensin-converting enzyme inhibitor derived from tuna muscle .

Kohama Y ; Oka H ; Murayama N ; Iida K ; Itoh M ; Itoh M ; Ying X ; Mimura T

Faculty of Pharmaceutical Sciences , Osaka University , Japan .

J Pharmacobiodyn 15 : 223-9 ( 1992)

Abstract
The influence of angiotensin-converting enzyme ( ACE ) inhibitory octapeptide derived from tuna muscle ( tuna AI ) on the bovine aorta endothelial cell ( BAEC ) migration was investigated , as compared with captopril . BAEC migration was quantitated 6 d after release from contact inhibition by a teflon fence assay . The culture grown in the presence of tuna AI ( 1 and 10 microM ) clearly exhibited an increase in migration , compared with the control . The media collected from tuna AI ( 1 and 10 microM)-stimulated BAECs significantly exhibited the interleukin ( IL ) -1 activity that was detected by the thymocyte costimulation assay with phytohemagglutinin . Although tuna AI was a weaker ACE inhibitor than captopril , the increasing effect of tuna AI on the migration and the IL-1 generation in BAECs was slightly greater than that of captopril . In quiescent BAECs , tuna AI ( 1 microM ) apparently induced c-myc and platelet derived growth factor ( PDGF ) A-chain messenger ribonucleic acid ( mRNA ) expressions within 30 min , which persisted for 6 h . In contrast , captopril induced a very low expression of c-myc mRNA , and had no relation to PDGF A-chain mRNA expression . These results suggest that the increase of BAEC migration by tuna AI , unlike captopril , is likely related to the induction or activation of IL-1 , and c-myc and PDGF mRNAs , in addition to the inhibition of the conversion of endogenous angiotensin I to angiotensin II .