Medizinische Universität Graz - Research portal
Selected Publication:
Stranzl, A; Schmidt, H; Winkler, R; Kostner, GM.
Low-density lipoprotein receptor mRNA in human breast cancer cells: influence by PKC modulators.
Breast Cancer Res Treat. 1997; 42(3):195-205
Doi: 10.1023%2FA%3A1005754026205
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- Leading authors Med Uni Graz
- Kostner Gerhard
- Co-authors Med Uni Graz
- Schmidt Helena
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Breast Neoplasms - enzymology
- Carcinogens - pharmacology
- Enzyme Activation - pharmacology
- Enzyme Inhibitors - pharmacology
- Gene Expression - pharmacology
- Humans - pharmacology
- Neoplasms, Hormone-Dependent - metabolism
- Protein Kinase C - antagonists and inhibitors
- RNA, Messenger - metabolism
- Receptors, Estrogen - metabolism
- Receptors, LDL - biosynthesis
- Ribonucleases - metabolism
- Tetradecanoylphorbol Acetate - pharmacology
- Tumor Cells, Cultured - pharmacology
- Find related publications in this database (Keywords)
- Low-Density Lipoprotein Receptor
- Messenger-RNA
- Phorbol Ester
- Protein Kinase C
- Human-Breast Cancer Cell Lines