WISP3 and RhoC guanosine triphosphatase cooperate in the development of inflammatory breast cancer

Breast Cancer Research

Sofia D Merajver¹  Zhi-Fen Wu¹  Mei Wu²  Gary Gallagher¹  Quintin Pan¹  Yanhong Zhang¹  Celina G Kleer¹ 

[1] Comprehensive Cancer Center, Univeristy of Michigan, Ann Arbor, MI, USA;Department of Internal Medicine, Univeristy of Michigan, Ann Arbor, MI, USA

关键词: WNT-pathway;    vascular endothelial growth factor;    tumor suppressor gene;    oncogene;    motility;    CCN proteins;   

Others  :  1118772
DOI  :  10.1186/bcr755

 received in 2003-06-17, accepted in 2003-12-05,  发布年份 2003

【 摘 要 】

Background

Inflammatory breast cancer (IBC) is the most lethal form of locally advanced breast cancer. We found concordant and consistent alterations of two genes in 90% of IBC tumors when compared with stage-matched non-IBC tumors: overexpression of RhoC guanosine triphosphatase and loss of WNT-1 induced secreted protein 3 (WISP3). Further work revealed that RhoC is a transforming oncogene for human mammary epithelial (HME) cells. Despite the aggressiveness of the RhoC-driven phenotype, it does not quantitatively reach that of the true IBC tumors. We have demonstrated that WISP3 has tumor growth and angiogenesis inhibitory functions in IBC. We proposed that RhoC and WISP3 cooperate in the development of IBC.

Methods

Using an antisense approach, we blocked WISP3 expression in HME cells. Cellular proliferation and growth were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and anchorage-independent growth in a soft agar assay. Vascular endothelial growth factor (VEGF) was measured in conditioned medium by enzyme-linked immunosorbent assay.

Results

Antisense inhibition of WISP3 in HME cells increased RhoC mRNA levels and resulted in an increase in cellular proliferation, anchorage-independent growth and VEGF levels in the conditioned medium. Conversely, restoration of WISP3 expression in the highly malignant IBC cell line SUM149 was able to decrease the expression of RhoC protein.

Conclusion

WISP3 modulates RhoC expression in HME cells and in the IBC cell line SUM149. This provides further evidence that these two genes act in concert to give rise to the highly aggressive IBC phenotype. We propose a model of this interaction as a starting point for further investigations.

【 授权许可】

   
2004 Kleer et al., licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 图 表 】

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