Transcriptome Analysis of Wnt3a-Treated Triple-Negative Breast Cancer Cells

Abstract

The canonical Wnt/β-catenin pathway is activated in triple-negative breast cancer (TNBC). The activation of this pathway leads to the expression of specific target genes depending on the cell/tissue context. Here, we analyzed the transcriptome of two different TNBC cell lines to define a comprehensive list of Wnt target genes. The treatment of cells with Wnt3a for 6h up-regulated the expression (fold change > 1.3) of 59 genes in MDA-MB-468 cells and 241 genes in HCC38 cells. Thirty genes were common to both cell lines. Beta-catenin may also be a transcriptional repressor and we found that 18 and 166 genes were down-regulated in response to Wnt3a treatment for 6h in MDA-MB-468 and HCC38 cells, respectively, of which six were common to both cell lines. Only half of the activated and the repressed transcripts have been previously described as Wnt target genes. Therefore, our study reveals 137 novel genes that may be positively regulated by Wnt3a and 104 novel genes that may be negatively regulated by Wnt3a. These genes are involved in the Wnt pathway itself, and also in TGFβ, p53 and Hedgehog pathways. Thorough characterization of these novel potential Wnt target genes may reveal new regulators of the canonical Wnt pathway. The comparison of our list of Wnt target genes with those published in other cellular contexts confirms the notion that Wnt target genes are tissue-, cell line- and treatment-specific. Genes up-regulated in Wnt3a-stimulated cell lines were more strongly expressed in TNBC than in luminal A breast cancer samples. These genes were also overexpressed, but to a much lesser extent, in HER2+ and luminal B tumors. We identified 72 Wnt target genes higher expressed in TNBCs (17 with a fold change >1.3) which may reflect the chronic activation of the canonical Wnt pathway that occurs in TNBC tumors.

LRP8 is overexpressed in estrogen‐negative breast cancers and a potential target for these tumors

“…Our cohort, comprising 35 luminal A (LA: ER + /HER2 − ), 40 luminal B (LB: ER + / HER2 + ), 46 TNBC (ER − /PR − / HER2 + ), 33 ER − /PR − /HER2 + , and 18 normal breast tissues, has been described elsewhere . The RNA microarray (Affymetrix U133 plus 2.0, Paris, France) results have also been reported elsewhere …”

Gene expression profiling of breast cancer in Lebanese women

“…Cell Intensity Data (CEL) files were generated using the Affymetrix GeneChip Command Console (AGCC) software version 3.2. Data used to represent the Western cohort were downloaded from the NCBI GEO database54. These comprised raw data files from two Affymetrix datasets - GSE6519455 and GSE256856.…”

Loss of Limb-Bud-and-Heart (LBH) attenuates mammary hyperplasia and tumor development in MMTV-Wnt1 transgenic mice

“…Importantly, LBH is abnormally overexpressed in MMTV-Wnt1 mammary tumors, and in human triple-negative breast cancers, correlating with WNT pathway hyperactivation [13, 19]. This, together with WNT inhibition studies, showing that endogenous LBH overexpression in TNBC cell lines is WNT-dependent [13], and a recent microarray study, identifying LBH as one of few WNT target genes rapidly and consistently induced by Wnt3a in TNBC cell lines [20], suggests a close link between LBH and WNT activation in breast cancer. Yet, the pathological roles of LBH in breast carcinogenesis and in WNT-mediated tumorigenesis have remained obscure.…”