Clinical & Experimental Metastasis

, Volume 19, Issue 4, pp 301–311

Mitogen activated protein kinase pathway is involved in RhoC GTPase induced motility, invasion and angiogenesis in inflammatory breast cancer

  • Kenneth L. van Golen
  • Li Wei Bao
  • Quintin Pan
  • Fred R. Miller
  • Zhi Fen Wu
  • Sofia D. Merajver
Article

DOI: 10.1023/A:1015518114931

Cite this article as:
van Golen, K.L., Wei Bao, L., Pan, Q. et al. Clin Exp Metastasis (2002) 19: 301. doi:10.1023/A:1015518114931

Abstract

Inflammatory breast cancer (IBC) is the most lethal form of locally advanced breast cancer known. IBC carries a guarded prognosis primarily due to rapid onset of disease, typically within six months, and the propensity of tumor emboli to invade the dermal lymphatics and spread systemically. Although the clinical manifestations of IBC have been well documented, until recently little was known about the genetic mechanisms underlying the disease. In a comprehensive study aimed at identifying the molecular mechanisms responsible for the unique IBC phenotype, our laboratory identified overexpression of RhoC GTPase in over 90% of IBC tumors in contrast to 36% of stage-matched non-IBC tumors. We also demonstrated that overexpression of RhoC GTPase in human mammary epithelial (HME) cells nearly recapitulated the IBC phenotype with regards to invasion, motility and angiogenesis. In the current study we sought to delineate which signaling pathways were responsible for each aspect of the IBC phenotype. Using well-established inhibitors to the mitogen activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K) pathways. We found that activation of the MAPK pathway was responsible for motility, invasion and production of angiogenic factors. In contrast, growth under anchorage independent conditions was dependent on the PI3K pathway.

angiogenic factors C3 exotransferase human mammary epithelial (HME) cells inflammatory breast cancer (IBC) inhibitors invasion mitogen activated protein kinase (MAPK) motility phosphatidylinositol-3 kinase (PI3K) RhoC GTPase 

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Kenneth L. van Golen
    • 1
  • Li Wei Bao
    • 1
  • Quintin Pan
    • 1
  • Fred R. Miller
    • 2
  • Zhi Fen Wu
    • 1
  • Sofia D. Merajver
    • 1
  1. 1.Department of Internal MedicineUniversity of Michigan Comprehensive Cancer CenterAnn ArborUSA
  2. 2.Breast Cancer ProgramBarbara Ann Karmanos Cancer InstituteDetroitUSA

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