Caveolin-1 inhibits epidermal growth factor-stimulated lamellipod extension and cell migration in metastatic mammary adenocarcinoma cells (MTLn3) - Transformation suppressor effects of adenovirus-mediated gene delivery of caveolin-1

Caveolin-1 is a principal component of caveolae membranes that may function as a transformation suppressor. For example, the human caveolin-1 gene is localized to a suspected tumor suppressor locus (D7S522; 7q31.1) that is de leted in human cancers, including mammary carcinomas. However, little is kn own about the role of caveolins in regulating cell movement, a critical par ameter in determining metastatic potential. Here, we examine the role of ca veolin-1 in cell movement. For this purpose, me employed an established cel lular model, MTLn3, a metastatic rat mammary adenocarcinoma cell line. In t his system, epidermal growth factor (EGF) stimulation induces rapid lamelli pod extension and cell migration. Interestingly, we find that MTLn3 cells f ail to express detectable levels of endogenous caveolin-1. To restore caveo lin-1 expression in MTLn3 cells efficiently, we employed an inducible adeno viral gene delivery system to achieve tightly controlled expression of cave olin-1. We show here that caveolin-1 expression in MTLn3 cells inhibits EGF -stimulated lamellipod extension and cell migration and blocks their anchor age-independent growth, Under these conditions, EGF-induced activation of t he p42/44 mitogen-activated protein kinase cascade is also blunted. Our res ults suggest that caveolin-1 expression in motile MTLn3 cells induces a non -motile phenotype.