title: A shift from normal to high glucose levels stimulates cell proliferation in drug sensitive MCF-7 human breast cancer cells but not in multidrug resistant MCF-7/ADR cells which overproduce PKC-betaII.
abstract: Glucose concentration may be an important factor in breast cancer cell proliferation because the prevalence of breast cancer is high in diabetic patients. To determine the role of protein kinase C (PKC)-betaII in regulating MCF-7 cell proliferation at different glucose concentrations, the effects of glucose and a PKC-betaII-specific inhibitor (CGP53353) were examined in cultures of MCF-7 human breast cancer cell line and its multidrug resistant variant (MCF-7/ADR). Cell proliferation and DNA synthesis of MCF-7 were increased when glucose concentration in the culture medium was increased from normal (5.5 mM) to high (25 mM) levels. However, MCF-7/ADR cell proliferation and DNA synthesis were unaffected by the increase in glucose. PKC-betaII protein and the corresponding mRNA levels were 4- to 5-fold higher in MCF-7/ADR than in MCF-7 cells. High glucose-induced decreases of PKC-betaII protein and mRNA levels were observed during the DNA synthesis phase in MCF-7 but not in MCF-7/ADR cells. Decreases in PKC-betaII mRNA and protein levels below a critical threshold in response to high glucose levels may account for glucose-stimulated proliferation of MCF-7 cells. Cultures of multidrug resistant MCF-7/ADR cells reach maximal cell density in medium containing normal (5.5 mM) glucose levels and are not induced to grow further in response to high (25 mM) glucose. Our results demonstrate a link between high glucose-induced PKC-betaII isozyme down-regulation with concomitant acceleration of cell cycle progression in MCF-7 cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of South Florida College of Medicine, Tampa, FL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: N A
authors.initials: NA
authors.lastname: Patel
authors.forename: J
authors.initials: J
authors.lastname: Taggart
authors.forename: R
authors.initials: R
authors.lastname: Sridhar
authors.forename: D R
authors.initials: DR
authors.lastname: Cooper
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008353:Mannitol / Q000494:pharmacology; D010797:Phthalimides / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010797:Phthalimides; D008353:Mannitol; D004247:DNA; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D005947:Glucose; C098874:4,5-dianilinophthalimide