Abstract |
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.
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Authors | L M Shaw, C Chao, U M Wewer, A M Mercurio |
Journal | Cancer research
(Cancer Res)
Vol. 56
Issue 5
Pg. 959-63
(Mar 01 1996)
ISSN: 0008-5472 [Print] United States |
PMID | 8640785
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- DNA, Complementary
- Integrin alpha6beta1
- Integrins
- Laminin
- Receptors, Laminin
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Topics |
- Breast Neoplasms
(metabolism, pathology)
- Cell Adhesion
- Cell Movement
- DNA, Complementary
(genetics)
- Female
- Gene Transfer Techniques
- Humans
- Integrin alpha6beta1
- Integrins
(genetics, metabolism)
- Laminin
(metabolism)
- Receptors, Laminin
(metabolism)
- Tumor Cells, Cultured
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