A Mutant High-Density Lipoprotein Receptor Inhibits Proliferation of Human Breast Cancer Cells

Abstract

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.

Tumor targeting effects of a novel modified paclitaxel-loaded discoidal mimic high density lipoproteins

“…This outcome may be explained as following: first, smaller nanocarrier size and longer half-life in vivo of cP-d-rHDL assisted in their accumulation in the tumors through EPR effect (passive targeting), which were consistent with previous reports (Jie et al, 2012;Lee et al, 2012). Second, SR-BI has been found to be broadly expressed in breast cancer cells, so drug from d-rHDL could be endocytosed into tumors via SR-BImediated mechanism (Cao et al, 2004;Zhang et al, 2013). Third, more apoA-I were conjugated to the lipid bilayer of cP-d-rHDL, thus contributing to striking enhancement in therapeutic efficacy (positive targeting).…”

Role of Lipoproteins in Carcinogenesis and in Chemoprevention

“…The targeted delivery of anticancer agents via lipoprotein carriers is based on the concept that cancer cells have a higher expression of lipoprotein receptors (Lacko et al, 2002;Cao et al, 2004) due to their increased need for cholesterol to promote rapid proliferation. Clinical studies have shown that HDL cholesterol levels, like LDL levels, are lower in cancer patients, including those with haematological malignancies (Fiorenza et al, 2000).…”

Prolactin regulatory element binding protein as a potential transcriptional factor for the insulin gene in response to glucose stimulation

“…The PREB expression vector was transfected into the cultured INS-1 cells by the conventional cationic liposome transfection method as described previously [18]. The transfected cells were selected by adding G418 to the media, and clones showing high PREB production were identified using western blot analysis.…”