Mechanism of Integrim-Mediated Growth Control in Normal, Transformed, and Neoplastic Breast Cells

摘要

Anchorage-dependent cell growth by normal cells and the loss of this dependence during tumorigenesis is a phenomenon that has been recognized for many years. The primary cell adhesion receptors that mediate binding to extracellular matrix proteins are integrins Our data suggest that alpha 3 beta 1 and alpha 6 beta 4 are the primary integrins responsible for mediating the G1/S transition in normal mammary epithelial cells and that these mechanisms may be defective in metastatic cancer cells. Other integrins also appear to influence components of the cell cycle regulatory machinery. For example, binding of GRGDS peptides to integrins (alpha v beta 5, alpha v beta 3, alpha 5 beta 1) on both normal and cancer cells appears to regulate the activities of cdc2 kinase and cyclinA-associated kinases. Cancer cells appear to have numerous defects in both cell adhesion components (alpha 6 beta 4, E-cadherin, laminin-5) and cell cycle regulatory components (cyclin D2, p21) which may contribute to the adhesion i independent phenotype. A difference in expression of the alternatively-spliced forms of the integrin alpha 6 beta 4, alpha 6A and alpha 6B, suggests that this marker may have diagnostic or prognostic value. Further study of the significance of these defects may lead to the development of novel therapeutics for the treatment or cure of breast cancer.