Function of the Integrin a6fJl in Metastatic Breast Carcinoma Cells Assessed by Expression of a Dominant-Negative Receptor'

The involvement of the a6@3lintegrin, a laminin receptor, in breast carcInoma progression needs to be addressed rigorously. We report that a human breast carcinoma cell lIne, MDA-MB.435, known to be highly Invasive and metastatic, expresses three potential Integrin laminin recep tors: a2fil, [email protected], and a6fil, but uses only a6@3lto mediate adhesion and migration on laminin matrices. To Investigate the contribution of a6@J1 to the aggressive behavior of these cells, we developed a dominant-negative strategy for knocking out a6fil function that involved expression of a cytoplasmic domain deletion mutant of the @34integrin subunit by cDNA transfection. Stable transfectants of MDA-MB-435 cells that expressed this mutant fi4 subunit were inhibited dramatically in their ability to adhere and migrate on laminin matrices, and their capacity to Invade Matrigel was reduced significantly. These findings support the hypothesis that a6@31is important for breast cancer progression. Moreover, this approach is a powerful method that should be useful in assessing the role of a6fil in other cells.