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MAPK Kinase 3 Is a Tumor Suppressor with Reduced Copy Number in Breast Cancer
- Source :
- Cancer Research. 74:162-172
- Publication Year :
- 2014
- Publisher :
- American Association for Cancer Research (AACR), 2014.
-
Abstract
- 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 mitogen–activated protein kinase (MAPK) MKK3 suppresses the growth of breast cancer, in which it varies in copy number. A pervasive loss of MKK3 gene copy number in patients with breast cancer 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. Cancer Res; 74(1); 162–72. ©2013 AACR.
- Subjects :
- MAPK/ERK pathway
Oncology
Cancer Research
medicine.medical_specialty
MAP Kinase Kinase 3
Gene Dosage
Breast Neoplasms
Mice, Transgenic
Biology
Mice
Breast cancer
Cell Line, Tumor
Internal medicine
medicine
Animals
Humans
RNA, Messenger
Copy-number variation
Protein kinase A
Kinase
Tumor Suppressor Proteins
Cell cycle
medicine.disease
Immunohistochemistry
Tumor progression
Cancer cell
Cancer research
Heterografts
Female
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 74
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....f6bff5cba570f5046c8d0ebe8de609a9