Abstract
Epithelial intercellular cohesion, mainly mediated by E-cadherin (CDH1) expression and function, may be deregulated during cancer cell invasion of adjacent tissues and lymphatic and vascular channels. CDH1 expression is down-modulated in invasive lobular breast carcinomas but its regulation in invasive ductal carcinomas (IDC) is less clear. CDH1 expression is repressed by transcription factors such as Snail (SNAI1) and its product is degraded after Hakai ubiquitination. We compared CDH1, SNAI1 and HAKAI mRNA expression in IDC and paired adjacent normal breast tissue and evaluated its relation with node metastasis and circulating tumor cells. Matched tumor/peritumoral and blood samples were collected from 30 patients with early IDC. Epithelial cells from each compartment (tumor/peritumoral) were recovered by an immunomagnetic method and gene expression was determined by real time RT-PCR. There were no differences in CDH1, SNAI1 and HAKAI mRNA expression between tumor and corresponding peritumoral samples and no differential tumoral gene expression according to nodal involvement. Another 30 patients with a long-term follow-up (at least 5 years) and a differential prognosis (good or poor, as defined by breast cancer death) had E-cadherin and Snail protein detected by immunohistochemistry in tumor samples. In this group, E-cadherin-positive expression, but not Snail, may be associated with a better prognosis. This is the first report simultaneously analyzing CDH1, SNAI1 and HAKAI mRNA expression in matched tumor and peritumoral samples from patients with IDC. However, no clear pattern of their expression could distinguish the invasive tumor compartment from its adjacent normal tissue.
Highlights
To invade, breast cancer cells reduce their intercellular cohesion, lose polarity, enhance their motility and proteolytic activity, and acquire mesenchymal cell characteristics, undergoing a dramatic remodeling of the cytoskeleton in a process similar to the epithelial-mesenchymal transition (EMT) that takes place during embryogenesis [1,2].Invasive carcinomas may spread through lymphatic or vascular channels and metastasize to regional lymph nodes and distant sites.Functional loss of E-cadherin (CDH1) in an epithelial cell has been considered a hallmark of EMT
CDH1 mRNA expression was evaluated in 22 paired samples and a positive correlation was detected between them (r = 0.697; P < 0.01; Pearson correlation); no differential expression between the primary tumor
Boxplots (Figure 4B) suggest that there was a trend towards a lower E-cadherin mRNA expression in tumor samples from these patients with circulating tumor cells
Summary
Breast cancer cells reduce their intercellular cohesion, lose polarity, enhance their motility and proteolytic activity, and acquire mesenchymal cell characteristics, undergoing a dramatic remodeling of the cytoskeleton in a process similar to the epithelial-mesenchymal transition (EMT) that takes place during embryogenesis [1,2].Invasive carcinomas may spread through lymphatic or vascular channels and metastasize to regional lymph nodes and distant sites.Functional loss of E-cadherin (CDH1) in an epithelial cell has been considered a hallmark of EMT. Breast cancer cells reduce their intercellular cohesion, lose polarity, enhance their motility and proteolytic activity, and acquire mesenchymal cell characteristics, undergoing a dramatic remodeling of the cytoskeleton in a process similar to the epithelial-mesenchymal transition (EMT) that takes place during embryogenesis [1,2]. Invasive carcinomas may spread through lymphatic or vascular channels and metastasize to regional lymph nodes and distant sites. Functional loss of E-cadherin (CDH1) in an epithelial cell has been considered a hallmark of EMT. CDH1 expression may be repressed by transcription factors such as Snail (SNAI1), ZEB1 and Slug [2,3,4]. Snail belongs to a family of zinc-finger-containing transcriptional repressors implicated in the regulation of the EMT phenomenon [5] and, Snail transfection into epithelial cells leads to a more.
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