Faculty Collaboration Database

Overexpression of protein kinase C-alpha in MCF-7 breast cancer cells results in differential regulation and expression of alphavbeta3 and alphavbeta5. Int J Oncol 1999 Jul;15(1):127-36

Date

06/22/1999

Pubmed ID

10375605

DOI

10.3892/ijo.15.1.127

Scopus ID

2-s2.0-0033160367 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

MCF-7 breast cancer cells stably transfected with protein kinase C-alpha (MCF-7-PKC-alpha cells) show anchorage-independent growth and exhibit increased tumorigenicity in nude mice. Since integrins are involved in tumor growth and metastatic spread, we investigated whether integrin expression is differentially regulated in MCF-7-PKC-alpha cells. Fluorescence-activated cell sorting revealed that alphavbeta3 is highly expressed on MCF-7-PKC-alpha cells, but is undetectable on MCF-7V cells (MCF-7 cells transfected with vector only). In contrast, MCF-7-PKC-alpha cells have reduced expression of alphavbeta5. Blocking experiments with antibodies to alphavbeta3 and alphavbeta5 revealed that these receptors are used by MCF-7-PKC-alpha cells to adhere primarily to vitronectin and osteopontin. Consistent with heterodimer expression, MCF-7-PKC-alpha cells express increased beta3 and decreased beta5 on their surface. Surface expression of alphav on MCF-7-PKC-alpha cells is unchanged. Western blotting, Northern analysis, and nuclear run-on assays indicated that post-translational mechanisms increase the surface expression of beta3 on MCF-7-PKC-alpha cells. In contrast, reduced beta5 transcription diminishes beta5 surface expression on MCF-7-PKC-alpha cells. These results indicate that overexpression of PKC-alpha in MCF-7 cells alters beta5 and beta3 expression by transcriptional and post-translational mechanisms, respectively, resulting in altered heterodimer expression. These findings suggest that the increased metastatic capacity of tumor cells with elevated protein kinase C levels may result, in part, from modulation of integrin expression.

Author List

Carey I, Williams CL, Ways DK, Noti JD

Author

Carol L. Williams PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Breast Neoplasms
Cell Adhesion
Dimerization
Enzyme Induction
Female
Gene Expression Regulation, Neoplastic
Humans
Integrins
Isoenzymes
Mice
Mice, Nude
Neoplasm Metastasis
Neoplasm Proteins
Neoplasm Transplantation
Osteopontin
Protein Kinase C
Protein Kinase C-alpha
Receptors, Vitronectin
Recombinant Fusion Proteins
Sialoglycoproteins
Tetradecanoylphorbol Acetate
Transcription, Genetic
Transfection
Tumor Cells, Cultured
Vitronectin