All-trans-Retinoic Acid-mediated Growth Inhibition Involves Inhibition of Human Kinesin-related Protein HsEg5

In this study we used differential display reverse transcription-polymerase chain reaction to search for differentially expressed all- trans -retinoic acid (ATRA)-responsive genes in pancreatic carcinoma cells. We identified the kinesin-related protein HsEg5, which plays an essential role in spindle...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-07, Vol.274 (27), p.18925-18931
Main Authors: Kaiser, A, Brembeck, F H, Nicke, B, Wiedenmann, B, Riecken, E O, Rosewicz, S
Format: Article
Language:English
Subjects:
Cell Cycle - drug effects
Cell Division - drug effects
Gene Expression Regulation - drug effects
HL-60 Cells
Humans
Keratinocytes - drug effects
Keratinocytes - metabolism
Kinesin - antagonists & inhibitors
Kinesin - genetics
Mitosis
Oligonucleotides, Antisense
Pancreatic Neoplasms - metabolism
Polymerase Chain Reaction
Protein Processing, Post-Translational
Transfection
Tretinoin - pharmacology
Tumor Cells, Cultured
Xenopus Proteins
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Summary:In this study we used differential display reverse transcription-polymerase chain reaction to search for differentially expressed all- trans -retinoic acid (ATRA)-responsive genes in pancreatic carcinoma cells. We identified the kinesin-related protein HsEg5, which plays an essential role in spindle assembly and spindle function during mitosis, as a novel molecule involved in ATRA-mediated growth inhibition. Using Northern and Western blot analysis we demonstrated that ATRA significantly inhibits HsEg5 expression in various pancreatic carcinoma cell lines as well as in HaCat keratinocytes. Inhibition of HsEg5 expression by ATRA occurs at the posttranscriptional level. As a consequence, tumor cells synchronized in S-phase revealed a retarded progression through G 2 /M phase of the cell cycle indicating that HsEg5 inhibition results in a delayed progression through mitosis. Furthermore, a significant decrease of HsEg5 protein expression achieved by antisense transfection revealed a significant growth inhibition compared with control cells. Therefore, HsEg5 represents a novel molecule involved in ATRA-mediated growth inhibition, suggesting that vitamin A derivatives can interact with the bipolar spindle apparatus during mitosis.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.274.27.18925