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.

• Authors: Wen M Cao, Koji Murao, Hitomi Imachi, Xiao Yu, Hiroshi Abe, Akira Yamauchi, Michio Niimi, Akira Miyauchi, Norman C W Wong, Toshihiko Ishida
• Journal: Cancer research (Cancer Res) Vol. 64 Issue 4 Pg. 1515-21 (Feb 15 2004) ISSN: 0008-5472 [Print] United States
• PMID: 14973113 (Publication Type: Journal Article)

Chemical References

• CD36 Antigens
• Carrier Proteins
• Lipoproteins, HDL
• Proto-Oncogene Proteins
• RNA-Binding Proteins
• Receptors, Immunologic
• Receptors, Lipoprotein
• Receptors, Scavenger
• SCARB1 protein, human
• Scavenger Receptors, Class B
• Transcription Factor AP-1
• high density lipoprotein receptors
• high density lipoprotein binding protein
• AKT1 protein, human
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Apoptosis
• Breast Neoplasms (drug therapy)
• CD36 Antigens (genetics)
• Carrier Proteins
• Cell Division
• Female
• Humans
• Lipoproteins, HDL (antagonists & inhibitors)
• Mutation
• Phosphatidylinositol 3-Kinases (physiology)
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins (physiology)
• Proto-Oncogene Proteins c-akt
• RNA-Binding Proteins
• Receptors, Immunologic
• Receptors, Lipoprotein (genetics, physiology)
• Receptors, Scavenger
• Scavenger Receptors, Class B
• Transcription Factor AP-1 (genetics)