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-βII
✍ Scribed by Mayumi Yamamoto; Niketa A. Patel; Jennifer Taggart; Rajagopalan Sridhar; Denise R. Cooper
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 651 KB
- Volume
- 83
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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)-II in regulating MCF-7 cell proliferation at different glucose concentrations, the effects of glucose and a PKC-II-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-II 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-II protein and mRNA levels were observed during the DNA synthesis phase in MCF-7 but not in MCF-7/ ADR cells. Decreases in PKC-II 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-II isozyme downregulation with concomitant acceleration of cell cycle progression in MCF-7 cells. Int.