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

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.

journal_name

Clin Exp Metastasis

journal_title

Clinical & experimental metastasis

authors

van Golen KL,Bao LW,Pan Q,Miller FR,Wu ZF,Merajver SD

doi

10.1023/a:1015518114931

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

301-11

issue

4

eissn

0262-0898

issn

1573-7276

journal_volume

19

pub_type

杂志文章

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