Breast Cancer Research and Treatment

, Volume 124, Issue 1, pp 49–61 | Cite as

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

  • 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
Preclinical study


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.


Gα12/13 Breast cell invasion MMP-2 p53 



Matrix metalloproteinase


Mitogen-activated protein kinase


MAPK kinase kinase


Extracellular signal-regulated kinase


c-Jun N-terminal protein kinase


Dominant negative



This study was supported by the KOSEF (MEST, No.R11-2007-107-01002-0), and by the KOSEF NRL Program (MEST, No. ROA-2008-000-20070-0). We thank Dr. Nae K. Sung (Core Institute of Medical Statistics, Seoul, Korea) for statistical analysis of the clinical data.


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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Eun-Sook Kim
    • 1
  • Jae-Boon Jeong
    • 1
  • Seonhoe Kim
    • 1
  • Kyung-Min Lee
    • 2
  • Eunyoung Ko
    • 2
  • Dong-Young Noh
    • 2
  • Ki-Tae Hwang
    • 3
  • Ji Hee Ha
    • 4
  • Chang Ho Lee
    • 5
  • Sang Geon Kim
    • 6
  • Aree Moon
    • 1
  1. 1.College of PharmacyDuksung Women’s UniversitySeoulKorea
  2. 2.Department of Cancer Biology and Cancer Reserch InstituteSeoul National University College of MedicineSeoulKorea
  3. 3.Department of SurgerySeoul National University, Boramae HospitalSeoulKorea
  4. 4.Cancer InstituteUniversity of OdlahomaOklahomaUSA
  5. 5.College of MedicineHanyang UniversitySeoulKorea
  6. 6.College of PharmacySeoul National UniversitySeoulKorea

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