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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2010

01-11-2010 | Preclinical study

The G12 family proteins upregulate matrix metalloproteinase-2 via p53 leading to human breast cell invasion

Authors: Eun-Sook Kim, Jae-Boon Jeong, Seonhoe Kim, Kyung-Min Lee, Eunyoung Ko, Dong-Young Noh, Ki-Tae Hwang, Ji Hee Ha, Chang Ho Lee, Sang Geon Kim, Aree Moon

Published in: Breast Cancer Research and Treatment | Issue 1/2010

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Abstract

Although mounting evidence suggests a role for G12 proteins, Gα12 and Gα13, in tumor progression, a direct role of G12 proteins has not been determined. This study aims to elucidate the molecular mechanism for a tumorigenic and invasive potential of Gα12 and Gα13 in MCF10A human breast epithelial cells. Here, we report, for the first time, that Gα12 and Gα13 induce upregulation of matrix metalloproteinase (MMP)-2 leading to the invasive and migratory phenotypes in MCF10A cells. We further show that p53 is an important transcription factor for induction of MMP-2 transcriptional activation by Gα12/13. Gα12/13-induced MMP-2 upregulation, invasion, and migration are dependent on the activation of Ras, Rac1, MKK3/6, p38, and Akt. Using human breast tissue samples, we demonstrate that the expression levels of Gα12 and MMP-2 are strongly correlated with the pathogenically diagnosed cancer (P < 0.0001). Moreover, the expression of Gα12 shows a strong correlation with that of MMP-2 in human breast cancer tissues, implicating the in vivo tumorigenic potential of Gα12. Taken together, this study elucidated the role of G12 proteins in regulating processes for MMP-2 expression and malignant phenotypic conversion of MCF10A human breast epithelial cells, providing a molecular basis for the promoting role of Gα12 and Gα13 in breast cell invasion.
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Metadata
Title
The G12 family proteins upregulate matrix metalloproteinase-2 via p53 leading to human breast cell invasion
Authors
Eun-Sook Kim
Jae-Boon Jeong
Seonhoe Kim
Kyung-Min Lee
Eunyoung Ko
Dong-Young Noh
Ki-Tae Hwang
Ji Hee Ha
Chang Ho Lee
Sang Geon Kim
Aree Moon
Publication date
01-11-2010
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-009-0697-2

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