Abstract |
The role of the integrin alpha 6 beta 1 in breast carcinoma progression was studied by targeted elimination of this integrin in MDA-MB-435 cells, a human breast carcinoma cell line that is highly metastatic in athymic mice. The strategy used is based on the finding that expression of a cytoplasmic domain deletion mutant of the beta 4-integrin subunit (beta 4-delta CYT) in MDA-MB-435 cells eliminates formation of the alpha 6 beta 1 heterodimer. MDA-MB-435 cells that lacked alpha 6 beta 1 expression (beta 4-delta CYT transfectants) formed tumors in athymic mice that were suppressed in their growth and that exhibited a significant increase in apoptosis in comparison to the control tumors. Unlike the control MDA-MB-435 cells, the beta 4-delta CYT transfectants were unable to establish metastatic foci in the lungs. Also, the control transfectants grew substantially better than the beta 4-delta CYT transfectants in the liver after intrahepatic injection because of extensive apoptosis in the beta 4-delta CYT transfectants. These data suggest that a major function of the alpha 6 beta 1 integrin in breast carcinoma is to facilitate tumorigenesis and promote tumor cell survival in distant organs.
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Authors | U M Wewer, L M Shaw, R Albrechtsen, A M Mercurio |
Journal | The American journal of pathology
(Am J Pathol)
Vol. 151
Issue 5
Pg. 1191-8
(Nov 1997)
ISSN: 0002-9440 [Print] United States |
PMID | 9358743
(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 |
- Integrin alpha6beta1
- Integrins
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Topics |
- Animals
- Breast Neoplasms
(pathology)
- Carcinoma
(pathology, physiopathology, secondary)
- Cell Survival
(drug effects)
- Female
- Gene Deletion
- Humans
- Integrin alpha6beta1
- Integrins
(deficiency, genetics, physiology)
- Mice
- Mice, Nude
- Neoplasm Transplantation
- Transfection
- Transplantation, Heterologous
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