Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profiles induced by knockdown and overexpression of p63 variants in MCF-10A mammary epithelial cell line


ABSTRACT: p63 is critical for epithelial development yet little is known about the transcriptional programmes it regulates. The p63 transactivating (TA) isoforms contain an amino-terminal exon that encodes a p53-like transactivation domain, whereas ΔN-isoforms lack this domain but contain the common DNA binding domain (DBD), suggesting that TAp63 and ΔNp63 isoforms may have opposing functions. By characterising transcriptional changes and cellular effects following modulation of p63 expression, we have defined a vital role for p63 in cellular adhesion. Knockdown of p63 expression caused downregulation of cell adhesion-associated genes, cell detachment and anoikis in mammary epithelial cells and keratinocytes. Conversely, overexpression of the TAp63γ or ΔNp63α isoforms of p63 upregulated cell adhesion molecules, increased cellular adhesion and conferred resistance to anoikis. Total RNA was isolated 48 h after retroviral or adenoviral infection and was subjected to reverse transcription, labelling and hybridization. The knockdown samples were performed in duplicate with shRNA vector control, shRNA targetting all isoforms of p63 (shDBD) and shRNA targetting p63 isoforms containing the transactivating (TA) domains. The overexpression samples were performed in triplicate with vector control, overexpression of the ΔNp63α isoform, and overexpression of the TAp63γ isoforms.

ORGANISM(S): Homo sapiens

SUBMITTER: Jason Carroll 

PROVIDER: E-GEOD-20286 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Dose-dependent induction of distinct phenotypic responses to Notch pathway activation in mammary epithelial cells.

Mazzone Marco M   Selfors Laura M LM   Albeck John J   Overholtzer Michael M   Sale Sanja S   Carroll Danielle L DL   Pandya Darshan D   Lu Yiling Y   Mills Gordon B GB   Aster Jon C JC   Artavanis-Tsakonas Spyros S   Brugge Joan S JS  

Proceedings of the National Academy of Sciences of the United States of America 20100301 11


Aberrant activation of Notch receptors has been implicated in breast cancer; however, the mechanisms contributing to Notch-dependent transformation remain elusive because Notch displays dichotomous functional activities, promoting both proliferation and growth arrest. We investigated the cellular basis for the heterogeneous responses to Notch pathway activation in 3D cultures of MCF-10A mammary epithelial cells. Expression of a constitutively active Notch-1 intracellular domain (NICD) was found  ...[more]

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