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MAPK kinase 3 is a tumor suppressor with reduced copy number in breast cancer.

Authors: Macneil, AJ  Jiao, SC  McEachern, LA  Yang, YJ  Dennis, A  Yu, H  Xu, Z  Marshall, JS  Lin, TJ 
Citation: Macneil AJ, etal., Cancer Res. 2013 Nov 14.
Pubmed: (View Article at PubMed) PMID:24233520
DOI: Full-text: DOI:10.1158/0008-5472.CAN-13-1310

Cancers are initiated as a result of changes that occur in the genome. Identification of gains and losses in the structure and expression of tumor suppressor genes and oncogenes lies at the root of the understanding of cancer cell biology. Here we show that the MAPK kinase MKK3 suppresses the growth of breast cancer where it varies in copy number. A pervasive loss of MKK3 gene copy number in breast cancer patients is associated with an impairment of MKK3 expression and protein level in malignant tissues. To assess the functional role of MKK3 in breast cancer, we showed in an animal model that MKK3 activity is required for suppression of tumor growth. Active MKK3 enhanced expression of the cyclin-dependent kinase inhibitors p21Cip1/Waf1 and p27Kip1, leading to increased cell cycle arrest in G1 phase of the cell cycle. Our results reveal the functional significance of MKK3 as a tumor suppressor and improve understanding of the dynamic role of the MAPK pathway in tumor progression.


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CRRD Object Information
CRRD ID: 7495808
Created: 2013-12-13
Species: All species
Last Modified: 2013-12-13
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.