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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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Published in: | The Journal of biological chemistry 1999-07, Vol.274 (27), p.18925-18931 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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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. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.274.27.18925 |