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C-Myc transforms human mammary epithelial cells through repression of the Wnt inhibitors DKK1 and SFRP1.

ABSTRACT: c-myc is frequently amplified in breast cancer; however, the mechanism of myc-induced mammary epithelial cell transformation has not been defined. We show that c-Myc induces a profound morphological transformation in human mammary epithelial cells and anchorage-independent growth. c-Myc suppresses the Wnt inhibitors DKK1 and SFRP1, and derepression of DKK1 or SFRP1 reduces Myc-dependent transforming activity. Myc-dependent repression of DKK1 and SFRP1 is accompanied by Wnt target gene activation and endogenous T-cell factor activity. Myc-induced mouse mammary tumors have repressed SFRP1 and increased expression of Wnt target genes. DKK1 and SFRP1 inhibit the transformed phenotype of breast cancer cell lines, and DKK1 inhibits tumor formation. We propose a positive feedback loop for activation of the c-myc and Wnt pathways in breast cancer.

SUBMITTER: Cowling VH

PROVIDER: S-EPMC1951955 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

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c-Myc transforms human mammary epithelial cells through repression of the Wnt inhibitors DKK1 and SFRP1.

Cowling Victoria H VH D'Cruz Celina M CM Chodosh Lewis A LA Cole Michael D MD

Molecular and cellular biology 20070507 14

c-myc is frequently amplified in breast cancer; however, the mechanism of myc-induced mammary epithelial cell transformation has not been defined. We show that c-Myc induces a profound morphological transformation in human mammary epithelial cells and anchorage-independent growth. c-Myc suppresses the Wnt inhibitors DKK1 and SFRP1, and derepression of DKK1 or SFRP1 reduces Myc-dependent transforming activity. Myc-dependent repression of DKK1 and SFRP1 is accompanied by Wnt target gene activation ...[more]

PMID: 17485441

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Mouse mammary tumor gene int-3: a member of the notch gene family transforms mammary epithelial cells.

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| S-EPMC289064 | biostudies-other

Down-regulation of SFRP1 in a mammary epithelial cell line

Project description:Microarray data to accompany Gauger et al. (2009) Cancer Cell International paper A treated X untreated design was used whereby immortalized human mammary epithelial cell lines (TERT cells) were modified to stably express an siRNA that knocked down SFRP1 expression. These "treated" cells were labeled with Cy5 and four replicate harvests were hybridized to Agilent 4by44k whole genome microarrays, along with a Cy3 labeled untreated control. The untreated control consisted of 4 pooled harvests of the parent cell line in normal growth conditions at 60-80% confluence.

2010-05-08 | E-GEOD-15948 | biostudies-arrayexpress

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