PCB-153 exposure coordinates cell cycle progression and cellular metabolism in human mammary epithelial cells

Venkatasubbaiah A VENKATESHA; Amanda L KALEN; Ehab H SARSOUR; Prabhat C GOSWAMI

doi:10.1016/j.toxlet.2010.04.005

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PCB-153 exposure coordinates cell cycle progression and cellular metabolism in human mammary epithelial cells

Journal article

Open access

Peer reviewed

PCB-153 exposure coordinates cell cycle progression and cellular metabolism in human mammary epithelial cells

Venkatasubbaiah A VENKATESHA, Amanda L KALEN, Ehab H SARSOUR and Prabhat C GOSWAMI

Toxicology letters, Vol.196(2), pp.110-116

2010

DOI: 10.1016/j.toxlet.2010.04.005

PMCID: PMC2891036

PMID: 20394812

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Abstract

2,2',4,4',5,5'-Hexachlorobiphenyl (PCB-153) is a non-metabolizable environmental chemical contaminant commonly found in breast milk of PCB exposed individuals, suggesting that chronic exposure to PCB-153 could have adverse health effects. We have shown previously that PCB-153 increased reactive oxygen species levels in non-tumorigenic MCF-10A human mammary epithelial cells, which were associated with DNA damage, growth inhibition, and cytotoxicity. This study investigates the hypothesis that PCB-153 exposure coordinates cell cycle progression and cellular metabolism by inhibiting cyclin D1 accumulation. PCB-153 treated MCF-10A cells exhibited a dose and time dependent decrease in cyclin D1 protein levels. The decrease in cyclin D1 protein levels was associated with an inhibition in AKT and GSK-3beta phosphorylation, which correlated with an increase in cyclin D1-T286 phosphorylation. Fibroblasts carrying a mutant form of cyclin D1 (T286A) were resistant to PCB-153 induced degradation of cyclin D1. Pre-treatment of cells with a proteasome inhibitor (MG132) suppressed PCB-153 induced decrease in cyclin D1 protein levels. Interestingly, suppression in cyclin D1 accumulation was associated with an increase in cellular glucose consumption, and hexokinase II and pyruvate kinase protein levels. These results suggest that cyclin D1 coordinates cell cycle progression and cellular metabolism in PCB-153 treated non-tumorigenic human mammary epithelial cells.

Toxicology

Biological and medical sciences

Medical sciences

Details

Title: Subtitle: PCB-153 exposure coordinates cell cycle progression and cellular metabolism in human mammary epithelial cells
Creators: Venkatasubbaiah A VENKATESHA - Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, 500 Newton Road, Iowa City, IA 52242-1181, United States
Amanda L KALEN - Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, 500 Newton Road, Iowa City, IA 52242-1181, United States
Ehab H SARSOUR - Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, 500 Newton Road, Iowa City, IA 52242-1181, United States
Prabhat C GOSWAMI - Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, 500 Newton Road, Iowa City, IA 52242-1181, United States
Resource Type: Journal article
Publication Details: Toxicology letters, Vol.196(2), pp.110-116
DOI: 10.1016/j.toxlet.2010.04.005
PMID: 20394812
PMCID: PMC2891036
NLM abbreviation: Toxicol Lett
ISSN: 0378-4274
eISSN: 1879-3169
Publisher: Elsevier; Shannon
Language: English
Date published: 2010
Academic Unit: Radiation Oncology
Record Identifier: 9984047857002771

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