PMID- 10427134 OWN - NLM STAT- MEDLINE DCOM- 19991014 LR - 20071115 IS - 1019-6439 (Print) IS - 1019-6439 (Linking) VI - 15 IP - 3 DP - 1999 Sep TI - The mitogen activated protein kinase pathway is required for proliferation but not invasion of human squamous cell carcinoma lines. PG - 519-23 AB - Growth factor receptors of the tyrosine kinase family regulate proliferation and migration of a variety of cell types. Binding of cognate ligands to these receptors induces multiple cellular responses, including cell cycle progression and motility in culture model systems. In stratified squamous epithelial cells, these receptors include epidermal growth factor receptor (EGFR) that binds both EGF and transforming growth factor alpha (TGFalpha), and c-met whose ligand is hepatocyte growth factor/scatter factor (HGF/SF). Intracellular signaling via these receptors occurs by several mechanisms, including activation of ras, phosphatidylinositol 3-kinase (PI3K), and the mitogen activated protein kinase (MAPK) pathways. Growth factor independence is a characteristic feature of transformation in cancer cells. Previous studies have shown that human squamous cell carcinoma (SCC) lines do not require EGF or TGFalpha for proliferation. We show that while these cell lines expressed EGFR and c-met, stimulation with their respective ligands did not induce proliferation but markedly increased invasion of reconstituted basement membranes. However, EGFR kinase activity was required for proliferation and EGF induced invasion by these cells. Signaling via ras, PI3K, and MAPK was required for proliferation of SCC lines. However, inhibition of ras and MAPK did not significantly reduce invasion by these cells nor completely block stimulation of this activity by EGF and HGF. We concluded that MAPK signaling was required for proliferation but not invasion of human SCC lines. FAU - Tsang, D K AU - Tsang DK AD - Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA. FAU - Crowe, D L AU - Crowe DL LA - eng GR - DE10966/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - Greece TA - Int J Oncol JT - International journal of oncology JID - 9306042 RN - 0 (Receptors, Growth Factor) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) SB - IM MH - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism MH - Carcinoma, Squamous Cell/*enzymology/pathology MH - Cell Division/physiology MH - Humans MH - Neoplasm Invasiveness MH - Receptors, Growth Factor/*physiology MH - Signal Transduction/physiology MH - Tumor Cells, Cultured EDAT- 1999/07/31 00:00 MHDA- 1999/07/31 00:01 CRDT- 1999/07/31 00:00 PHST- 1999/07/31 00:00 [pubmed] PHST- 1999/07/31 00:01 [medline] PHST- 1999/07/31 00:00 [entrez] PST - ppublish SO - Int J Oncol. 1999 Sep;15(3):519-23.