Adherence to osteopontin via alphavbeta3 suppresses phorbol ester-mediated apoptosis in MCF-7 breast cancer cells that overexpress protein kinase C-alpha.

Noti,J D

doi:10.3892/ijo.17.6.1237

Dec 2000 Volume 17 Issue 6

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Dec 2000 Volume 17 Issue 6

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Article

Adherence to osteopontin via alphavbeta3 suppresses phorbol ester-mediated apoptosis in MCF-7 breast cancer cells that overexpress protein kinase C-alpha.

Authors:
- J D Noti
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Affiliations: Laboratory of Molecular Biology, Guthrie Research Institute, One Guthrie Square, Sayre, PA 18840, USA. jnoti@inet.guthrie.org
Pages: 1237-1280
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Published online on: December 1, 2000

https://doi.org/10.3892/ijo.17.6.1237
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Abstract

Overexpression of protein kinase C-alpha in MCF-7 breast cancer cells (MCF-7-PKC-alpha cells) results in anchorage-independent growth and increased tumorigenicity of these cells in nude mice. MCF-7-PKC-alpha cells, unlike their parental MCF-7 cells, are sensitized to apoptosis by phorbol esters. When adhered to osteopontin, a bone matrix protein, MCF-7-PKC-alpha cells were resistant to phorbol ester mediated apoptosis. Fluorescence-activated cell sorting revealed that osteopontin receptors, alphavbeta3 and alphavbeta5, are expressed on MCF-7-PKC-alpha cells and that both are used to adhere to osteopontin. Addition of an RGD-containing peptide inhibited survival of MCF-7-PKC-alpha cells exposed to phorbol ester and adhered to osteopontin. This indicated that an integrin was involved in the cell death suppression signal. Whereas, anti-alphavbeta5 antibody did not reduce survival of MCF-7-PKC-alpha cells adhered to osteopontin, anti-alphavbeta3 antibody could efficiently block suppression of apoptosis. Phorbol ester also induced increased expression of alphavbeta3 on MCF-7-PKC-alpha cells by upregulating expression of a second species of beta3 mRNA. This study suggests that breast cancer cells that have metastasized to bone may have a survival advantage resulting from interaction of alphavbeta3 on these cells with the bone protein osteopontin.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Adherence to osteopontin via alphavbeta3 suppresses phorbol ester-mediated apoptosis in MCF-7 breast cancer cells that overexpress protein kinase C-alpha.

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