A. Stranzl et al., LOW-DENSITY-LIPOPROTEIN RECEPTOR MESSENGER-RNA IN HUMAN BREAST-CANCERCELLS - INFLUENCE BY PKC MODULATORS, Breast cancer research and treatment, 42(3), 1997, pp. 195-205
It was reported previously that low-density lipoproteins (LDL) differe
ntially 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 analysi
s in ER- (MDA-MB-231 and HBL-100) and ER+ (MCF-7 and ZR75-1) cells, an
d compared them with the estrogen receptor (ER) status. Measurable amo
unts of ER mRNA were only found in ER+ cells as expected. LDL-R mRNA a
bundance was 3-5 fold higher in ER- cells as compared to ER+ cells. In
cubation with phorbol-12-myristate-13-acetate led to a significant inc
rease (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 dio
ctanoylglycerol, 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-bre
ast cancer the process of conversion from hormone-responsive to hormon
e-unresponsive status is accompanied by a change in PKC activity and P
KC might exert cell specific differences on the regulation of LDL-R mR
NA levels, which in turn influences the delivery of exogenous choleste
rol to cancer cells.