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Molecular Cancer

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Open Access 01-12-2007 | Research

Expression of LIM kinase 1 is associated with reversible G1/S phase arrest, chromosomal instability and prostate cancer

Authors: Monica Davila, Darshana Jhala, Debashis Ghosh, William E Grizzle, Ratna Chakrabarti

Published in: Molecular Cancer | Issue 1/2007

Abstract

Background

LIM kinase 1 (LIMK1), a LIM domain containing serine/threonine kinase, modulates actin dynamics through inactivation of the actin depolymerizing protein cofilin. Recent studies have indicated an important role of LIMK1 in growth and invasion of prostate and breast cancer cells; however, the molecular mechanism whereby LIMK1 induces tumor progression is unknown. In this study, we investigated the effects of ectopic expression of LIMK1 on cellular morphology, cell cycle progression and expression profile of LIMK1 in prostate tumors.

Results

Ectopic expression of LIMK1 in benign prostatic hyperplasia cells (BPH), which naturally express low levels of LIMK1, resulted in appearance of abnormal mitotic spindles, multiple centrosomes and smaller chromosomal masses. Furthermore, a transient G1/S phase arrest and delayed G2/M progression was observed in BPH cells expressing LIMK1. When treated with chemotherapeutic agent Taxol, no metaphase arrest was noted in these cells. We have also noted increased nuclear staining of LIMK1 in tumors with higher Gleason Scores and incidence of metastasis.

Conclusion

Our results show that increased expression of LIMK1 results in chromosomal abnormalities, aberrant cell cycle progression and alteration of normal cellular response to microtubule stabilizing agent Taxol; and that LIMK1 expression may be associated with cancerous phenotype of the prostate.

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Title: Expression of LIM kinase 1 is associated with reversible G1/S phase arrest, chromosomal instability and prostate cancer
Authors: Monica Davila
Darshana Jhala
Debashis Ghosh
William E Grizzle
Ratna Chakrabarti
Publication date: 01-12-2007
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2007
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/1476-4598-6-40

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