High-density lipoprotein (HDL) stimulates the growth of many types of cells, including those of
breast cancer. High levels of HDL are associated with an increased risk of
breast cancer development. A
scavenger receptor of the B class (SR-BI)/human homolog of SR-BI, CD36, and LIMPII analogous-1 (CLA-1) facilitates the cellular uptake of
cholesterol from HDL and thus augments cell growth. Furthermore, HDL is also believed to have antiapoptotic effects on various cell types, and this feature adds to its ability to promote cell growth. These collaborative roles of HDL and CLA-1 prompted us to assess the function of these components on human
breast cancer cells. In this study, we created a mutant CLA-1 (
mCLA) that lacked the COOH-terminal tail to determine its potential role in
breast cancer cell growth. Expression of
mCLA inhibited the proliferation of
breast cancer cell line MCF-7. This inhibitory action of
mCLA required the transcriptional factor
activator protein-1 (AP-1), and the mutant receptor also affected the antiapoptotic features of HDL. The effect of HDL on
AP-1 activation and [(3)H]
thymidine incorporation was abrogated by
wortmannin, a specific inhibitor of
phosphoinositide 3-kinase. Furthermore, the dominant negative mutant of Akt abolished the ability of HDL to activate
AP-1. These findings raise the possibility that the inhibitors of the effects of HDL may be of therapeutic value for
breast cancer.