Association of increased basement membrane invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines

Thompson, Erik W.; Paik, Soonmyoung; Brünner, Nils; Sommers, Connie L.; Zugmaier, Gerhard; Clarke, Robert; Shima, Thomas B.; Torri, Jeffrey A.; Donahue, Steven; Lippman, Marc E.; Martin, George R.; Dickson, Robert B.

doi:10.1002/jcp.1041500314

Cited by 465 publications

(411 citation statements)

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“…Even though the correlation between a reorganisation of E-cadherin/b-catenin complexes and MCP-1 expression has never been reported before, the large amount of data from the literature, associating E-cadherin/b-catenin complexes reorganization and the expression of an invasive phenotype 20,22,[40][41][42][43][44] strengthen our findings. Furthermore, our data are in agreement with data reporting MCP-1 expression in a variety of human tumour cell lines including gastric, 10 ovarian, 45 breast, 9 melanoma, 46 pancreatic 7 and neuroblastoma cancer cell lines.…”

Section: Discussionsupporting

confidence: 79%

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Transactivation of MCP‐1/CCL2 by β‐catenin/TCF‐4 in human breast cancer cells

Mestdagt

Polette

Butticè

et al. 2005

Intl Journal of Cancer

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The loss of E-cadherin expression and the translocation of b-catenin to the nucleus are frequently associated with the metastatic conversion of epithelial cells. In the nucleus, b-catenin binds to the TCF/LEF-1 (T-cell factor/ lymphoid enhancer factor) transcription factor family resulting in the activation of several genes, some of them having important implications in tumour progression. In our study, we investigated the potential regulation of monocyte chemotactic protein-1 (MCP-1/CCL2) expression by the b-catenin/TCF pathway. This CC-chemokine has been implicated in tumour progression events such as angiogenesis or tumour associated macrophage (TAM) infiltration. We thus demonstrated that MCP-1 expression correlates with the reorganization of the E-cadherin/b-catenin complexes. Indeed, MCP-1 was expressed by invasive breast cancer cells (MDA-MB-231, BT549 and Hs578T), which do not express E-cadherin but was not produced by noninvasive breast cancer cell lines (MCF7 and T47D) expressing high level of E-cadherin. In addition, the MCP-1 promoter was activated in BT549 breast cancer cells transfected with b-catenin and TCF-4 cDNAs. The MCP-1 mRNA level was similarly upregulated. Moreover, we showed that MCP-1 mRNA was downregulated after transfection with a siRNA against b-catenin in both BT549 and Hs578T cells. Our results therefore identify MCP-1 as a target of the b-catenin/TCF/LEF pathway in breast tumour cells, a regulation which could play a key role in breast tumour progression. ' 2005 Wiley-Liss, Inc.Key words: MCP-1; b-catenin; breast cancer Chemokines constitute a superfamily of proinflammatory cytokines that are implicated in tumour progression, modulating not only host tumour-specific immunological response but also angiogenesis or tumour cell invasion and proliferation. 1-3 Monocyte chemotactic protein-1 (MCP-1) or CCL2 is a CC-chemokine that specifically attracts monocytes and memory T cells. It has been particularly implicated in processes characterized by mononuclear cell infiltration including breast cancer. 4,5 In some models, MCP-1 has been shown to display an antitumoral effect. 6,7 Nevertheless, a large number of studies demonstrate that MCP-1 facilitates tumour progression through its ability to recruit stromal cells including tumour associated macrophages (TAMs) and endothelial cells. 7-10 A pro-angiogenic role of MCP-1 has been demonstrated in many systems, facilitating tumour growth and dissemination. 8,9,11,12 Moreover, a direct effect of MCP-1 on tumour cell migration in vitro has also been described. 13 Recently, Lebrecht et al. 14 have correlated an increased MCP-1 serum level with an advanced breast tumour stage and the presence of lymph node metastasis. In the same way, Amann et al. 15 reported a significant association between MCP-1 urinary levels and tumour stage and grade. They suggested a use of its urinary level as prognosis marker in bladder cancer. The correlation between MCP-1 expression and a poor prognosis was also demonstrated for the squamous cell carcinoma of the oeso...

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Section: Discussionsupporting

confidence: 79%

“…[41][42][43] Examining MCP-1 mRNA expression by RT-PCR analysis, we observed that invasive, E-cadherin-negative cell lines (MDA-MB-231, BT549 and Hs578T) expressed high levels of MCP-1, whereas noninvasive, E-cadherin-positive cell lines (MCF7 and T47D) did not express MCP-1 mRNA (Fig. 1a).…”

Section: Mcp-1 Is Expressed By Invasive E-cadherin-negative Breast Cmentioning

confidence: 94%

Transactivation of MCP‐1/CCL2 by β‐catenin/TCF‐4 in human breast cancer cells

Mestdagt

Polette

Butticè

et al. 2005

Intl Journal of Cancer

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“…The fibroblastic phenotype of the cell lines in the latter cluster is strongly indicative of EMT. This is also supported by the increased invasiveness of these cell lines (BT549, Hs578T, MDA-MB-231 and MDA-MB-435s) in vitro and their metastatic potential in mouse models (Price et al, 1990;Thompson et al, 1992;Sommers et al, 1994a). Lacroix and Leclercq (2004) identified 72 differentially expressed genes between the (weakly) luminal epithelial and mesenchymal cell lines of which 15 genes (21%) coincide with differentially expressed genes in our 'Epithelial' vs 'Fibroblastic' cluster and are indicated in Tables 2 -4 with an asterisk.…”

Section: Discussionmentioning

confidence: 89%

E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines

et al. 2006

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Using genome-wide expression profiling of a panel of 27 human mammary cell lines with different mechanisms of E-cadherin inactivation, we evaluated the relationship between E-cadherin status and gene expression levels. Expression profiles of cell lines with E-cadherin (CDH1) promoter methylation were significantly different from those with CDH1 expression or, surprisingly, those with CDH1 truncating mutations. Furthermore, we found no significant differentially expressed genes between cell lines with wild-type and mutated CDH1. The expression profile complied with the fibroblastic morphology of the cell lines with promoter methylation, suggestive of epithelial -mesenchymal transition (EMT). All other lines, also the cases with CDH1 mutations, had epithelial features. Three non-tumorigenic mammary cell lines derived from normal breast epithelium also showed CDH1 promoter methylation, a fibroblastic phenotype and expression profile. We suggest that CDH1 promoter methylation, but not mutational inactivation, is part of an entire programme, resulting in EMT and increased invasiveness in breast cancer. The molecular events that are part of this programme can be inferred from the differentially expressed genes and include genes from the TGFb pathway, transcription factors involved in CDH1 regulation (i.e. ZFHX1B, SNAI2, but not SNAI1, TWIST), annexins, AP1/2 transcription factors and members of the actin and intermediate filament cytoskeleton organisation.

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“…Many epithelial cells express cytokeratin proteins K8, K18 and K19 (Oshima et al, 1988). Overexpression of cytokeratins with vimentin can lead to increased cell migration (Thompson et al, 1992;Chu et al, 1996), while overexpression of a dominant negative mutant K18 has been reported to reduce migratory ability in melanoma cells (Hendrix et al, 1992). These data raise the possibility that BAG-1 may promote cell migration through cooperation with these cytoskeletal proteins.…”

Section: Discussionmentioning

confidence: 99%