Low-density lipoprotein receptor mRNA in human breast cancer cells: influence by PKC modulators.
It was reported previously that low-density lipoproteins (LDL) differentially stimulate cell growth of hormone-responsive (ER+) and hormone-unresponsive (ER-) mammary tumor cell lines. Here we examined the mRNA levels of the LDL-receptor (LDL-R) gene with RNAse protection analysis in ER- (MDA-MB-231 and HBL-100) and ER+ (MCF-7 and ZR75-1) cells, and compared them with the estrogen receptor (ER) status. Measurable amounts of ER mRNA were only found in ER+ cells as expected. LDL-R mRNA abundance was 3-5 fold higher in ER- cells as compared to ER+ cells. Incubation with phorbol-12-myristate-13-acetate led to a significant increase (p < 0.005) of LDL-R mRNA in ER+ cells, whereas in ER- cells LDL-R mRNA levels remained merely unchanged. Incubation of cells with dioctanoylglycerol, a synthetic homolog of diacylglycerol, increased LDL-R mRNA in ER+ but not in ER-. Inhibition of protein kinase C (PKC) by H7 resulted in a highly significant reduction of LDL-R mRNA both in ER+ and ER- cells. PKC seems to be an important regulator of LDL-R mRNA abundance in mammary tumor cells. It is hypothesized that in human-breast cancer the process of conversion from hormone-responsive to hormone-unresponsive status is accompanied by a change in PKC activity and PKC might exert cell specific differences on the regulation of LDL-R mRNA levels, which in turn influences the delivery of exogenous cholesterol to cancer cells.
Stranzl
A
A
Medical Biochemistry, University of Graz, Austria.
Schmidt
H
H
Winkler
R
R
Kostner
G M
GM
D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism*; D002273:Carcinogens / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011973:Receptors, LDL / Q000096:biosynthesis*; D012260:Ribonucleases / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011973:Receptors, LDL; D011493:Protein Kinase C; D012260:Ribonucleases; D013755:Tetradecanoylphorbol Acetate