Lineage Infidelity of MDA-MB-435 Cells

371

271

Section: Discussionmentioning

confidence: 99%

MicroRNA-125b Confers the Resistance of Breast Cancer Cells to Paclitaxel through Suppression of Pro-apoptotic Bcl-2 Antagonist Killer 1 (Bak1) Expression

Zhou

Liu

Zhao

et al. 2010

371

271

“…Extensive work from the M. D. Anderson Cancer Center shows that these cells express breast-specific (nonmelanocyte) markers and can be induced to secrete milk proteins and lipids (56). Furthermore, these cells preferentially grow when implanted into mammary fat pads compared with subcutaneous injection (57), similar to other breast cancers but unlike melanoma cell lines.…”

Section: Discussionmentioning

confidence: 99%

Integrin α6β4 Controls the Expression of Genes Associated with Cell Motility, Invasion, and Metastasis, Including S100A4/Metastasin

Chen

Sinha

Luxon

et al. 2009

148

140

The integrin ␣6␤4 is associated with carcinoma progression by contributing to apoptosis resistance, invasion, and metastasis, due in part to the activation of select transcription factors. To identify genes regulated by the ␣6␤4 integrin, we compared gene expression profiles of MDA-MB-435 cells that stably express integrin ␣6␤4 (MDA/␤4) and vector-only-transfected cells (MDA/mock) using Affymetrix GeneChip analysis. Our results show that integrin ␣6␤4 altered the expression of 538 genes (p < 0.01). Of these genes, 36 are associated with pathways implicated in cell motility and metastasis, including S100A4/ metastasin. S100A4 expression correlated well with integrin ␣6␤4 expression in established cell lines. Suppression of S100A4 by small interference RNA resulted in a reduced capacity of ␣6␤4-expressing cells to invade a reconstituted basement membrane in response to lysophosphatidic acid. Using small interference RNA, promoter analysis, and chromatin immunoprecipitation, we demonstrate that S100A4 is regulated by NFAT5, thus identifying the first target of NFAT5 in cancer. In addition, several genes that are known to be regulated by DNA methylation were up-regulated dramatically by integrin ␣6␤4 expression, including S100A4, FST, PDLIM4, CAPG, and Nkx2.2. Notably, inhibition of DNA methyltransferases stimulated expression of these genes in cells lacking the ␣6␤4 integrin, whereas demethylase inhibitors suppressed expression in ␣6␤4 integrin-expressing cells. Alterations in DNA methylation were confirmed by bisulfate sequencing, thus suggesting that integrin ␣6␤4 signaling can lead to the demethylation of select promoters. In summary, our data suggest that integrin ␣6␤4 confers a motile and invasive phenotype to breast carcinoma cells by regulating proinvasive and prometastatic gene expression.Integrins are receptors for the extracellular matrix, which have two major functions. The first is an adhesive function that secures cells to the surrounding extracellular matrix or, in the case of cell motility, provides traction for locomotion. Their second function is to transduce signals that are essential for cells to sense and integrate cues from the extracellular matrix, which include signals for directed cell motility, anchorage-dependent survival, and growth (1). As a result, integrin signaling and function are critical for most biological events in higher eukaryotes, both under normal and pathological conditions. In recent years, one integrin species, the ␣6␤4 integrin, has garnered much attention for its ability to promote an invasive and metastatic phenotype in carcinomas.In cells of epithelial origin, the integrin ␣6␤4 nucleates the formation of hemidesmosomes that link the cytokeratin cytoskeleton to the laminins found in the basement membrane, which are essential for epithelial integrity (2). During wound healing or the epithelial to mesenchymal transition (EMT), 2 the ␣6␤4 integrin is phosphorylated, is released from hemidesmosomes, and then binds the actin cytoskeleton (3). Under these conditions, the ␣6␤4...

“…Additionally, Daoy cells also express EagII naturally, which provided a good internal control. The third cell line, MDA-MB435S, is derived from a pleural effusion of a mammary carcinoma, although it seems more related to melanomas rather than carcinomas as revealed by gene array experiments (36,37) and expresses a lower amount of EagI (1000 -5000 copies/l). MDA-MB435S cells also express small amounts of EagII.…”

Section: Discussionmentioning

confidence: 99%

Silencing the Activity and Proliferative Properties of the Human EagI Potassium Channel by RNA Interference

Weber

Queiroz

Downie

et al. 2006

117

118

EagI potassium channels are natively expressed in the mammalian brain as well as in many cancer cell lines and tumor tissues. The role of EagI in malignant transformation has been suggested by several experiments, but the lack of specific EagI inhibitors has made it difficult to examine the influence of the channel on oncogenesis and its potential as a therapeutic target. We have used short interfering RNA to test the effects of EagI reduction on the behavior of tumor cells in vitro. By generating and optimizing an EagI-specific short interfering RNA system, we were able to study the effects of EagI depletion on several cancer cell lines that endogenously express this protein. We show here that our short interfering RNA sequences act specifically on EagI, reproducibly induce a significant decrease in the proliferation of tumor cell lines, and do not trigger any observable nonspecific responses.