Insulin-resistant MDA-MB231 human breast cancer cells contain a tyrosine kinase inhibiting activity.
In most human breast cancer cell lines, insulin, via its own receptor, stimulates cell growth. However, in MDA-MB231 breast cancer cells, insulin at concentration as high as 100 nM has no effect on cell growth, although insulin receptors (IRs) are overexpressed in these cells (29.1 ng IR/10(6) cells), and IR binding characteristics are similar to other breast cancer cell lines. IR tyrosine kinase activity is markedly reduced both in intact MDA-MB231 cells and in isolated IRs purified on a wheat germ agglutinin affinity column. MDA-MB231 cells contain a factor that inhibits both basal and insulin-stimulated IR tyrosine kinase activity in a concentration-dependent manner. This inhibitory activity copurifies with the IR on insulin-Sepharose affinity chromatography and is also effective against the tyrosine kinase activity of the IR-related insulin-like growth factor-I receptor and the oncoprotein v-abl but is ineffective against c-src tyrosine kinase activity. It is possible, therefore, that this tyrosine kinase inhibitor plays a role in regulating the mitogenic potential of the IR in some human breast cancers.
Costantino
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A
Cattedra di Endocrinologia, University of Catania, Italy.
Milazzo
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G
Giorgino
F
F
Russo
P
P
Goldfine
I D
ID
Vigneri
R
R
Belfiore
A
A
D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011972:Receptor, Insulin / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016895:Culture Media, Serum-Free; D007328:Insulin; D009363:Neoplasm Proteins; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin