Essential role for ALCAM gene silencing in megakaryocytic differentiation of K562 cells

Fang Tan; Samit Ghosh; Flaubert Mbeunkui; Robert Thomas; Joshua A Weiner; Solomon F Ofori-Acquah

doi:10.1186/1471-2199-11-91

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Essential role for ALCAM gene silencing in megakaryocytic differentiation of K562 cells

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Essential role for ALCAM gene silencing in megakaryocytic differentiation of K562 cells

Fang Tan, Samit Ghosh, Flaubert Mbeunkui, Robert Thomas, Joshua A Weiner and Solomon F Ofori-Acquah

BMC molecular biology, Vol.11(1), 91

12/02/2010

DOI: 10.1186/1471-2199-11-91

PMCID: PMC3003670

PMID: 21126364

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Abstract

Background Activated leukocyte cell adhesion molecule (ALCAM/CD166) is expressed by hematopoietic stem cells. However, its role in hematopoietic differentiation has not previously been defined. Results In this study, we show that ALCAM expression is silenced in erythromegakaryocytic progenitor cell lines. In agreement with this finding, the ALCAM promoter is occupied by GATA-1 in vivo, and a cognate motif at -850 inhibited promoter activity in K562 and MEG-01 cells. Gain-of-function studies showed that ALCAM clusters K562 cells in a process that requires PKC. Induction of megakaryocytic differentiation in K562 clones expressing ALCAM activated PKC-δ and triggered apoptosis. Conclusions There is a lineage-specific silencing of ALCAM in bi-potential erythromegakaryocytic progenitor cell lines. Marked apoptosis of ALCAM-expressing K562 clones treated with PMA suggests that aberrant ALCAM expression in erythromegakaryocytic progenitors may contribute to megakaryocytopenia.

Details

Title: Subtitle: Essential role for ALCAM gene silencing in megakaryocytic differentiation of K562 cells
Creators: Fang Tan - Department of Biology, The University of Iowa, Iowa City, IA 52242, USA
Samit Ghosh - Department of Biology, The University of Iowa, Iowa City, IA 52242, USA
Flaubert Mbeunkui - Department of Biology, The University of Iowa, Iowa City, IA 52242, USA
Robert Thomas - Department of Biology, The University of Iowa, Iowa City, IA 52242, USA
Joshua A Weiner - Department of Biology, The University of Iowa, Iowa City, IA 52242, USA
Solomon F Ofori-Acquah - Department of Biology, The University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: BMC molecular biology, Vol.11(1), 91
DOI: 10.1186/1471-2199-11-91
PMID: 21126364
PMCID: PMC3003670
NLM abbreviation: BMC Mol Biol
ISSN: 1471-2199
eISSN: 1471-2199
Publisher: BioMed Central
Language: English
Date published: 12/02/2010
Academic Unit: Liberal Arts and Science Admin; Psychiatry; Iowa Neuroscience Institute; Biology
Record Identifier: 9983997986402771

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