Shaw L M, Chao C, Wewer U M, Mercurio A M
Deaconess Hospital, Boston, Massachusetts 02115, USA.
Cancer Res. 1996 Mar 1;56(5):959-63.
The involvement of the alpha 6 beta a integrin, 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 receptors: alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 1, but uses only alpha 6 beta 1 to mediate adhesion and migration on laminin matrices. To investigate the contribution of alpha 6 beta 1 to the aggressive behavior of these cells, we developed a dominant-negative strategy for knocking out alpha 6 beta 1 function that involved expression of a cytoplasmic domain deletion mutant of the beta 4 integrin subunit by cDNA transfection. Stable transfectants of MDA-MB-435 cells that expressed this mutant beta 4 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 alpha 6 beta 1 is important for breast cancer progression. Moreover, this approach is a powerful method that should be useful in assessing the role of alpha 6 beta 1 in other cells.
α6β1整合素（一种层粘连蛋白受体）在乳腺癌进展中的作用需要进行严格研究。我们报告称，一种已知具有高度侵袭性和转移性的人乳腺癌细胞系MDA-MB-435表达三种潜在的整合素层粘连蛋白受体：α2β1、α3β1和α6β1，但仅利用α6β1介导在层粘连蛋白基质上的黏附和迁移。为了研究α6β1对这些细胞侵袭行为的作用，我们开发了一种显性负性策略来敲除α6β1的功能，该策略通过cDNA转染涉及β4整合素亚基细胞质结构域缺失突变体的表达。表达这种突变β4亚基的MDA-MB-435细胞稳定转染体在层粘连蛋白基质上黏附和迁移的能力受到显著抑制，其侵袭基质胶的能力也明显降低。这些发现支持了α6β1对乳腺癌进展很重要的假说。此外，这种方法是一种强大的手段，应该有助于评估α6β1在其他细胞中的作用。
