Caveolin-1 and Drug Responsiveness in Breast Cancer

Caveolins (CAVs) constitute a family of proteins that are principally responsible for the formation of caveolae, flaskshaped invaginations of the plasma membrane. Currently, there are three known caveolins: caveolin-1(CAV1), caveolin-2(CAV2), and caveolin-3 (CAV3). CAV1 was the first of the CAVs to be discovered (originally cloned as VIP21 in canines) [1]. CAV1 is an integral membrane protein that possesses a functional scaffolding domain used to collect, organize, and concentrate various signaling molecules. Through the use of a moncoclonal antibody [2], CAV1 was detected to be a structural component of caveolae, which had been the subject of many studies since their discovery by electron microscopy [3]. Caveolae are the flask shaped invaginations of the plasma membrane; they are about 50-100nm in diameter, and are a specific type of membrane lipid raft important in a variety of cellular functions. Lipid rafts are distinguished from the plasma membrane by their composition. Lipid rafts contain around 3-5 times the amount of cholesterols, as well as possessing around a 50% increase in the concentration of sphingolipids [4]. Important in signal transduction, these lipid rafts compartmentalize and concentrate signaling molecules that undergo endocytosis and are used to alter regulatory processes in the cell [5-7]. Caveolae are unique in that they are primarily formed due to the activity of the CAV proteins [2]. Approximately, 100-200 CAV proteins can be found in individual caveola [8].