Biomaterial Database

Phorbol ester reduces phosphorylation of epidermal growth factor receptor in pancreatic cancer cells by activation of a tyrosine phosphatase. 1999

J J Ho, and E R Farrelly, and Y S Kim

Veterans Medical Center, University of California, San Francisco, California, 94121, USA. jjl@itsa.ucsf.edu

In this study we report that phorbol 12-myristate 13-acetate (PMA) transiently reduced the level of EGF receptor tyrosine phosphorylation in three pancreatic cancer cell lines (HPAC, SW1990, and UCVA-1) in response to EGF. The effect was maximal at 40-90 min. Pretreatment with the protein kinase C inhibitor GF 109203X reduced the PMA effect. Flow cytometry experiments showed that PMA produced only a slight reduction in the surface expression of EGF-R. The phosphotyrosine phosphatase inhibitor bpV(phen) returned phosphorylation to almost control levels. Moreover, homogenates of PMA treated pancreatic cells reduced the phosphorylation of activated receptor that was immunoprecipitated from A431 epidermoid cells. A combination of orthovanadate and NaF or bpV(phen) inhibited the effect of the homogenates. These results suggest that PMA activates a phosphotyrosine phosphatase activity that reduces the steady-state level of tyrosine phosphorylation of the receptor that is induced by EGF.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D009942	Organometallic Compounds	A class of compounds of the type R-M, where a C atom is joined directly to any other element except H, C, N, O, F, Cl, Br, I, or At. (Grant & Hackh's Chemical Dictionary, 5th ed)	Metallo-Organic Compound,Metallo-Organic Compounds,Metalloorganic Compound,Organometallic Compound,Metalloorganic Compounds,Compound, Metallo-Organic,Compound, Metalloorganic,Compound, Organometallic,Compounds, Metallo-Organic,Compounds, Metalloorganic,Compounds, Organometallic,Metallo Organic Compound,Metallo Organic Compounds
D010190	Pancreatic Neoplasms	Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).	Cancer of Pancreas,Pancreatic Cancer,Cancer of the Pancreas,Neoplasms, Pancreatic,Pancreas Cancer,Pancreas Neoplasms,Pancreatic Acinar Carcinoma,Pancreatic Carcinoma,Acinar Carcinoma, Pancreatic,Acinar Carcinomas, Pancreatic,Cancer, Pancreas,Cancer, Pancreatic,Cancers, Pancreas,Cancers, Pancreatic,Carcinoma, Pancreatic,Carcinoma, Pancreatic Acinar,Carcinomas, Pancreatic,Carcinomas, Pancreatic Acinar,Neoplasm, Pancreas,Neoplasm, Pancreatic,Neoplasms, Pancreas,Pancreas Cancers,Pancreas Neoplasm,Pancreatic Acinar Carcinomas,Pancreatic Cancers,Pancreatic Carcinomas,Pancreatic Neoplasm
D010618	Phenanthrolines		Phenanthroline
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D011799	Quinazolines	A group of aromatic heterocyclic compounds that contain a bicyclic structure with two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring.	Quinazoline
D002462	Cell Membrane	The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.	Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man