PMID- 12469196 OWN - NLM STAT- MEDLINE DCOM- 20030616 LR - 20181130 IS - 1019-6439 (Print) IS - 1019-6439 (Linking) VI - 22 IP - 1 DP - 2003 Jan TI - Protein kinase C-alpha activation by phorbol ester induces secretion of gelatinase B/MMP-9 through ERK 1/2 pathway in capillary endothelial cells. PG - 137-43 AB - In the present study, phorbol 12-myristate 13-acetate (PMA) was found to increase secretion of matrix metalloproteinase (MMP)-9 and in vitro invasion in bovine capillary endothelial (BCE) cells, which were blocked by specific inhibitors of protein kinase C (PKC). To elucidate molecular mechanisms involved, we studied the effect of PMA on the activation of mitogen activated protein kinases (MAPKs), and found that PMA activated extracellular signal-regulated kinase (ERK)1/2 and PD98059, a specific inhibitor of MAPK kinase, significantly reduced PMA-induced MMP-9 secretion as well as in vitro invasion of BCE cells. Treatment of safingol, a specific PKC-alpha inhibitor, and introduction of antisense PKC-alpha into these cells reduced the secretion of MMP-9 and activation of ERK1/2 by PMA. Furthermore, we employed adenoviral PKC-alpha and found that weak PMA stimulation (5 ng/ml) enhanced ERK1/2 activation and MMP-9 secretion in these cells. Therefore, we strongly suggest that PKC-alpha, partly at least, have a crucial role in MMP-9 secretion and invasion of BCE cells which are mediated via ERK1/2 signaling pathway. FAU - Park, Myung-Jin AU - Park MJ AD - Laboratory of Cell Biology, Korea Cancer Center Hospital, 139-706 Seoul, Korea. FAU - Park, In-Chul AU - Park IC FAU - Lee, Hyung-Chan AU - Lee HC FAU - Woo, Sang-Hyeok AU - Woo SH FAU - Lee, Jae-Young AU - Lee JY FAU - Hong, Young-Joon AU - Hong YJ FAU - Rhee, Chang-Hun AU - Rhee CH FAU - Lee, Yun-Sil AU - Lee YS FAU - Lee, Seung-Hoon AU - Lee SH FAU - Shim, Bum-Sang AU - Shim BS FAU - Kuroki, Toshino AU - Kuroki T FAU - Hong, Seok-Il AU - Hong SI LA - eng PT - Journal Article PL - Greece TA - Int J Oncol JT - International journal of oncology JID - 9306042 RN - 0 (Flavonoids) RN - 0 (Imidazoles) RN - 0 (Pyridines) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.13 (Protein Kinase C-alpha) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - OU13V1EYWQ (SB 203580) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Animals MH - Capillaries/cytology/enzymology MH - Cattle MH - Endothelium, Vascular/cytology/*enzymology MH - Enzyme Activation MH - Flavonoids/pharmacology MH - Imidazoles/pharmacology MH - Matrix Metalloproteinase 9/*metabolism MH - Mitogen-Activated Protein Kinase 1/*physiology MH - Mitogen-Activated Protein Kinase 3 MH - Mitogen-Activated Protein Kinases/*physiology MH - Protein Kinase C/*physiology MH - Protein Kinase C-alpha MH - Pyridines/pharmacology MH - Tetradecanoylphorbol Acetate/*pharmacology EDAT- 2002/12/07 04:00 MHDA- 2003/06/17 05:00 CRDT- 2002/12/07 04:00 PHST- 2002/12/07 04:00 [pubmed] PHST- 2003/06/17 05:00 [medline] PHST- 2002/12/07 04:00 [entrez] PST - ppublish SO - Int J Oncol. 2003 Jan;22(1):137-43.