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Series GSE31322 Query DataSets for GSE31322
Status Public on Mar 20, 2012
Title Activation of different signaling pathways in the regulation of biological properties of human pancreatic cancer cells by the mucin MUC4 and the oncogenic receptor ErbB2 genes
Organism Homo sapiens
Experiment type Expression profiling by array
Summary The mucin MUC4 and its membrane partner the ErbB2 oncogenic receptor are potential actors and partners in pancreatic tumourigenesis. However, the way they function is still largely unknown. We thus undertook in this work to identify the cellular mechanisms and the intracellular signalling pathways under the control of both ErbB2 and MUC4. Using co-immunoprecipitation, we show that MUC4 and ErbB2 interact in the human pancreatic adenocarcinomatous cell line CAPAN-2. Stable Knocked-Down (KD) cellular clones for both MUC4 and ErbB2 were raised by a shRNA approach. Biological properties of these cells were then studied in vitro and in vivo. Our results show that ErbB2-KD cells are more apoptotic and less proliferative (decreased cyclin D1 and increased p27kip1 expression) while migration and invasive properties were not altered. MUC4-KD clones were less proliferative with decreased cyclin D1 expression, G1 cell cycle arrest and altered ErbB2/ErbB3 expression. Their migration properties were reduced whereas invasive properties were increased. Importantly, inhibition of ErbB2 and MUC4 expression did not impair the same signalling pathways (inhibition of MUC4 expression affected the JNK pathway whereas that of ErbB2 altered the MAPK pathway). Finally, ErbB2-KD and MUC4-KD cells showed impaired tumour growth in vivo. This indicates that ErbB2 and MUC4, that physically interact, activate different intracellular signalling pathways to regulate biological properties of pancreatic cancer cells. Altogether, these data bring new information regarding molecular mechanisms under the control of both MUC4 and ErbB2 that will have to be taken into account for developing efficient targeting of both proteins in order to slow down/stop pancreatic tumourigenesis.
Overall design profiling of pancreatic cells depleted for ErbB2 and MUC4
Contributor(s) Jonckheere N
Citation(s) 22393391
Submission date Aug 10, 2011
Last update date Feb 22, 2018
Contact name frédéric leprêtre
Organization name Lille University
Department CHU of Lille, CBP
Lab plateforme de génomique fonctionnelle et structurale
Street address Boulevard du Pr Leclercq
City lille
ZIP/Postal code 59037
Country France
Platforms (1)
GPL4133 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version)
Samples (8)
GSM776568 ErbB2-KD1
GSM776569 ErbB2-KD2
GSM776570 ErbB2-KD3
BioProject PRJNA146097

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE31322_RAW.tar 41.3 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table
Processed data provided as supplementary file

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