Specific down-regulation of annexin II expression in human cells interferes with cell proliferation

The protein-tyrosine kinase substrate annexin II is a growth regulated gene whose expression is increased in several human cancers. While the precise function of this protein is not understood, annexin II is proposed to be involved in multiple physiological activities, including DNA synthesis and ce...

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Veröffentlicht in:Molecular and cellular biochemistry 1999-09, Vol.199 (1-2), p.139-147
Hauptverfasser: Chiang, Y, Rizzino, A, Sibenaller, Z A, Wold, M S, Vishwanatha, J K
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container_end_page 147
container_issue 1-2
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container_title Molecular and cellular biochemistry
container_volume 199
creator Chiang, Y
Rizzino, A
Sibenaller, Z A
Wold, M S
Vishwanatha, J K
description The protein-tyrosine kinase substrate annexin II is a growth regulated gene whose expression is increased in several human cancers. While the precise function of this protein is not understood, annexin II is proposed to be involved in multiple physiological activities, including DNA synthesis and cell proliferation. Targeted disruption of the annexin II gene affects calcium signaling, tyrosine phosphorylation and apoptosis, indicating the important physiological role of this protein. We used a transient co-transfection assay to regulate annexin II expression in human HeLa, 293 and 293T cells, and measured the effects of annexin II down regulation on DNA synthesis and proliferation. Transfection of cells with an antisense annexin II vector results in inhibition of cell division and proliferation, with concomitant reduction in annexin II message and protein levels. Cellular DNA synthesis is significantly reduced in antisense transfected cells. Replication extracts made from antisense transfected cells have significantly reduced efficiency to support SV40 in vitro DNA replication, while the extracts made from sense transfected cells are fully capable of replication. Our results indicate an important role of annexin II in cellular DNA synthesis and cell proliferation.
doi_str_mv 10.1023/A:1006942128672
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subjects Annexin A2 - genetics
Annexin A2 - metabolism
Apoptosis
Cell division
Cell Division - genetics
Cells, Cultured
Deoxyribonucleic acid
DNA
DNA - biosynthesis
DNA Replication
DNA, Antisense - genetics
Down-Regulation
Gene Expression Regulation
HeLa Cells - metabolism
Humans
Kinases
Physiology
Promoter Regions, Genetic
Proteins
RNA, Messenger - metabolism
Simian virus 40 - genetics
title Specific down-regulation of annexin II expression in human cells interferes with cell proliferation
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