A role for protein kinase C delta in the differential sensitivity of MCF-7 and MDA-MB 231 human breast cancer cells to phorbol ester-induced growth arrest and p21(WAFI/CIP1) induction

M Shanmugam; N L Krett; E T Maizels; F M Murad; S T Rosen; M Hunzicker-Dunn

doi:10.1016/S0304-3835(01)00602-4

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A role for protein kinase C delta in the differential sensitivity of MCF-7 and MDA-MB 231 human breast cancer cells to phorbol ester-induced growth arrest and p21(WAFI/CIP1) induction

Journal article

Peer reviewed

A role for protein kinase C delta in the differential sensitivity of MCF-7 and MDA-MB 231 human breast cancer cells to phorbol ester-induced growth arrest and p21(WAFI/CIP1) induction

M Shanmugam, N L Krett, E T Maizels, F M Murad, S T Rosen and M Hunzicker-Dunn

Cancer letters, Vol.172(1), pp.43-53

10/22/2001

DOI: https://doi.org/10.1016/S0304-3835(01)00602-4

Handle:

https://hdl.handle.net/2376/106655

PMID: 11595128

Abstract

Receptors, Estrogen - metabolism

Tetradecanoylphorbol Acetate

Luciferases - metabolism

Humans

Dose-Response Relationship, Drug

Cytosol - enzymology

Carcinogens

Cyclins - biosynthesis

Transfection

Acetophenones - pharmacology

Cell Membrane - metabolism

Tumor Cells, Cultured

Benzopyrans - pharmacology

Protein Kinase C-delta

Isoenzymes - physiology

Detergents - pharmacology

Protein Kinase C - physiology

Cyclin-Dependent Kinase Inhibitor p21

Cells, Cultured

Enzyme Inhibitors - pharmacology

Rats

Breast Neoplasms - drug therapy

Blotting, Western

Cell Division - drug effects

Cell Membrane - enzymology

Animals

Plasmids

Protein Isoforms

Enzyme Activation

Octoxynol - pharmacology

The goal of this study was to investigate the differential sensitivity of estrogen receptor (ER) positive MCF-7 and ER negative MDA-MB 231 breast cancer cells to phorbol myristate acetate (PMA)-dependent growth arrest. MCF-7 cells were growth arrested by 80% while MDA-MB 231 cells were arrested by 20% in response to seven days of treatment with 10 nM PMA. Coincident with the increased sensitivity of MCF-7 cells to be growth arrested by the protein kinase C (PKC) activator PMA, PMA induced 9-fold higher levels of the cyclin dependent kinase (Cdk) inhibitor p21(WAF1/GIP1) in MCF-7 compared to MDA-MB 231 cells. A comparison of the PKC isoforms expressed in MCF-7 versus MDA-MB 231 cells showed that only the PMA-sensitive PKC delta and eta isoforms were expressed at markedly (> or =10-fold) elevated levels in MCF7 versus MDA-MB 231 cells. These results suggested that the differential sensitivity to growth arrest and induction of p2l(WAFl/CIPl) could reflect, at least in part, increased expression of PMA-dependent PKC isoforms delta and/or eta. Direct evidence to support this hypothesis was provided by the ability of transient transfections into MCF-7 cells of constitutively active PKC delta but not of PKC's eta or alpha or epsilon to enhance p21(WAFl/CIP1) promoter activity. These results suggest that PKC delta plays a fundamental role in the regulation of growth in estrogen receptor positive breast cancer cells.

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Title: A role for protein kinase C delta in the differential sensitivity of MCF-7 and MDA-MB 231 human breast cancer cells to phorbol ester-induced growth arrest and p21(WAFI/CIP1) induction
Creators: M Shanmugam - Department of Cell and Molecular Biology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA
N L Krett
E T Maizels
F M Murad
S T Rosen
M Hunzicker-Dunn
Publication Details: Cancer letters, Vol.172(1), pp.43-53
Academic Unit: Molecular Biosciences, School of
Publisher: Ireland
Grant note: P30 CA60553 / NCI NIH HHS
Identifiers: 99900546800901842
Language: English
Resource Type: Journal article

A role for protein kinase C delta in the differential sensitivity of MCF-7 and MDA-MB 231 human breast cancer cells to phorbol ester-induced growth arrest and p21(WAFI/CIP1) induction

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