Breast Cancer Research and Treatment

, Volume 95, Issue 3, pp 219–228 | Cite as

Overexpression of caveolin-1 and -2 in cell lines and in human samples of inflammatory breast cancer

  • Gert G. Van den Eynden
  • Steven J. Van  Laere
  • Ilse Van der  Auwera
  • Sofia D. Merajver
  • Eric A. Van  Marck
  • Peter van  Dam
  • Peter B. Vermeulen
  • Luc Y. Dirix
  • Kenneth L. van  Golen
Article

Summary

Purpose

Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer (LABC). The IBC phenotype is characterized by an infiltrative growth pattern, increased (lymph)angiogenesis and the propensity to invade dermal lymphatics. In pancreatic cancer, interactions between caveolin-1 and RhoC GTPase, a key molecule in causing the IBC phenotype, regulate tumour cell motility and invasion. In this study we sought to investigate the role of caveolin-1 and -2 in IBC cell lines and in human IBC samples.

Experimental design

Differential methylation techniques identified the methylation status of the caveolin-1 and -2 promoters in human mammary epithelial cells (HMECs) and the SUM149 cell line. In cell line experiments, caveolin-1 and -2 mRNA and protein expression were compared in HMECs, MCF10A, the SUM102 non-IBC cell lines and 2 IBC cell lines (SUM149 and SUM190). Furthermore, caveolin-1 and -2 mRNA and protein expression were compared in human IBC and non-IBC samples using cDNA microarray, real-time qRT-PCR and immunohistochemistry. Results were correlated with RhoC protein expression data.

Results

In the SUM149 cell line, the caveolin-1 and -2 promoter sites were hypomethylated. A significantly increased expression of caveolin-1 and -2, both at the mRNA and protein level was found in IBC cell lines and in human samples of IBC: caveolin-1 and -2 mRNA were respectively 1.7 (p = 0.02) and 2.2 (p = 0.03) fold more expressed in IBC compared to non IBC and at the protein level, 41.4% of IBC specimens expressed either caveolin-1 or -2, compared to 15.6% of non-IBC specimens (p = 0.03). Furthermore a correlation was found between RhoC protein expression and caveolin-1 (p = 0.1) or caveolin-2 (p = 0.09) or either caveolin-1 or -2 protein expression (p = 0.04).

Conclusions

Although considered a tumour suppressor in breast cancer, we demonstrated overexpression of caveolin-1 and -2 in IBC cell lines and in human samples of IBC, most likely due to hypomethylation of their respective promoters. These results confirm the distinct molecular signature of IBC. Our data further suggest interaction between RhoC GTPase and the caveolins in IBC.

Keywords

caveolin-1 caveolin-2 inflammatory breast cancer methylation RhoC GTPase 

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Copyright information

© Springer 2005

Authors and Affiliations

  • Gert G. Van den Eynden
    • 1
  • Steven J. Van  Laere
    • 1
  • Ilse Van der  Auwera
    • 1
  • Sofia D. Merajver
    • 2
  • Eric A. Van  Marck
    • 1
  • Peter van  Dam
    • 1
  • Peter B. Vermeulen
    • 1
  • Luc Y. Dirix
    • 1
  • Kenneth L. van  Golen
    • 2
  1. 1.Translational Cancer Research Group Antwerp, (Lab PathologyUniversity of Antwerp/University Hospital Antwerp, Edegem; Oncology Center, General Hospital St-AugustinusWilrijk)Belgium
  2. 2.Department of Internal Medicine, Division of Hematology and OncologyThe University of Michigan Comprehensive Cancer CenterAnn ArborUSA

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