Epidermal growth factor suppresses induction by progestin of the adhesion protein desmoplakin in T47D breast cancer cells

Breast Cancer Research

Lee E Faber³  Mariam Al-Dhaheri²  Brian G Rowan²  Haiyan Pang¹ 

[1] Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA;Department of Biochemistry and Molecular Biology, Medical College of Ohio, Toledo, Ohio, USA;Department of Physiology and Molecular Medicine, Medical College of Ohio, Toledo, USA

关键词: progesterone;    differential display RT-PCR;    epidermal growth factor;    desmoplakin;    breast cancer;   

 received in 2003-06-19, accepted in 2004-02-26,  发布年份 2004

【 摘 要 】

Introduction

Although the effects of progesterone on cell cycle progression are well known, its role in spreading and adhesion of breast cancer cells has not attracted much attention until recently. Indeed, by controlling cell adhesion proteins, progesterone may play a direct role in breast cancer invasion and metastasis. Progesterone has also been shown to modulate epidermal growth factor (EGF) effects in neoplasia, although EGF effects on progesterone pathways and targets are less well understood. In the present study we identify an effect of EGF on a progesterone target, namely desmoplakin.

Methods

Initially flow cytometry was used to establish the growing conditions and demonstrate that the T47D breast cancer cell line was responding to progesterone and EGF in a classical manner. Differential display RT-PCR was employed to identify differentially expressed genes affected by progesterone and EGF. Western and Northern blotting were used to verify interactions between EGF and progesterone in three breast cancer cell lines: T47D, MCF-7, and ZR-75.

Results

We found the cell adhesion protein desmoplakin to be upregulated by progesterone – a process that was suppressed by EGF. This appears to be a general but not universal effect in breast cancer cell lines.

Conclusion

Our findings suggest that progesterone and EGF may play opposing roles in metastasis. They also suggest that desmoplakin may be a useful biomarker for mechanistic studies designed to analyze the crosstalk between EGF and progesterone dependent events. Our work may help to bridge the fields of metastasis and differentiation, and the mechanisms of steroid action.

【 授权许可】

   
2004 Pang 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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