Differential Expression of Key Signaling Proteins in MCF10 Cell Lines, a Human Breast Cancer Progression Model.

Abstract

Breast cancer is a heterogeneous disease that develops through a multistep process whose molecular basis remains poorly understood. The molecular mechanisms of breast cancer progression have been extensively studied using the MCF10 model. We summarized recent results on differential expression of proteins in the MCF10 cell series - MCF10A, MCF10AT1, MCF10DCIS.com and MCF10CA1a - and compared the ability of the latter 3 lines to form tumors in immunodeficient mice. In addition, we also investigated expression of several key signaling proteins in the MCF10 cell series corresponding to different stages of breast cancer progression. MCF10DCIS.com and MCF10CA1a cells were highly tumorigenic; MCF10CA1a cells showed more aggressive tumor growth than MCF10DCIS.com cells. HRAS-driven cancer initiation stage was accompanied by the increased expression of c-Myc, cyclin D1 and IGF-IR. Tumorigenic cell lines expressed higher levels of pErk, pAkt, Stat3 and Pak4 compared to nontumorigenic cells. The expression of CD44v, CD44v3, CD44v6, ERBB2, Cox2 and Smad4 correlated with the increased tumorigenicity of the MCF10 cell lines. The differences in expression of signaling proteins involved in breast cancer progression may provide new insight into the mechanisms of tumorigenesis and useful information for development of targeted therapeutics.