Article

Identification and testing of a gene expression signature of invasive carcinoma cells within primary mammary tumors

Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Cancer Research (Impact Factor: 9.33). 01/2005; 64(23):8585-94. DOI: 10.1158/0008-5472.CAN-04-1136
Source: PubMed

ABSTRACT

We subjected cells collected using an in vivo invasion assay to cDNA microarray analysis to identify the gene expression profile of invasive carcinoma cells in primary mammary tumors. Expression of genes involved in cell division, survival, and cell motility were most dramatically changed in invasive cells indicating a population that is neither dividing nor apoptotic but intensely motile. In particular, the genes coding for the minimum motility machine that regulates beta-actin polymerization at the leading edge and, therefore, the motility and chemotaxis of carcinoma cells, were dramatically up-regulated. However, ZBP1, which restricts the localization of beta-actin, the substrate for the minimum motility machine, was down-regulated. This pattern of expression implicated ZBP1 as a suppressor of invasion. Reexpression of ZBP1 in metastatic cells with otherwise low levels of ZBP1 reestablished normal patterns of beta-actin mRNA targeting and suppressed chemotaxis and invasion in primary tumors. ZBP1 reexpression also inhibited metastasis from tumors. These experiments support the involvement in metastasis of the pathways identified in invasive cells, which are regulated by ZBP1.

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Available from: Sumanta Goswami
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    • "It facilitates cell invasion via phosphatidylinositol 3-kinase- dependent local accumulation of actin filaments [32]. Increased ENAH/Mena expression levels correlate with invasiveness of breast and salivary gland tumors[33, 34], and are also seen in colorectal cancer and in polyps with high grade dysplasia [35]. TNS1 (up-regulated 14-fold), which is also known as Tensin 1, has actin cross-linking activity and localizes to focal adhesions. "
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    • "Thus, to facilitate analysis of the mechanism of Mena INV dependent growth factor sensitization, we used human cell lines that ectopically express GFP- Mena, GFP-Mena INV , or GFP alone. Mena was found to be upregulated approximately 10-fold at the RNA level in invasive tumor cells collected from primary xenograft tumors, therefore we engineered our cells to express levels roughly comparable to those seen in invasive cells from primary tumors (Wang et al., 2004) (Fig S1). As expected, Mena INV -expressing cells invaded further into 3D collagen gels (Fig 1A). "
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