Title

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

Authors

Authors

M. Davila; D. Jhala; D. Ghosh; W. E. Grizzle;R. Chakrabarti

Comments

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Abbreviated Journal Title

Mol. Cancer

Keywords

CENTROSOME ABNORMALITIES; COFILIN PHOSPHORYLATION; ACTIN DYNAMICS; PROTEIN-KINASE; CELL-GROWTH; PDZ DOMAIN; ACTIVATION; LIM-KINASE-1; PROGRESSION; IDENTIFICATION; Biochemistry & Molecular Biology; Oncology

Abstract

Background: LIM kinase I (LIMKI), 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 LIMKI in growth and invasion of prostate and breast cancer cells; however, the molecular mechanism whereby LIMKI induces tumor progression is unknown. In this study, we investigated the effects of ectopic expression of LIMKI on cellular morphology, cell cycle progression and expression profile of LIMKI in prostate tumors. Results: Ectopic expression of LIMKI in benign prostatic hyperplasia cells (BPH), which naturally express low levels of LIMKI, resulted in appearance of abnormal mitotic spindles, multiple centrosomes and smaller chromosomal masses. Furthermore, a transient GI/S phase arrest and delayed G2/M progression was observed in BPH cells expressing LIMKI. When treated with chemotherapeutic agent Taxol, no metaphase arrest was noted in these cells. We have also noted increased nuclear staining of LIMKI in tumors with higher Gleason Scores and incidence of metastasis. Conclusion: Our results show that increased expression of LIMKI results in chromosomal abnormalities, aberrant cell cycle progression and alteration of normal cellular response to microtubule stabilizing agent Taxol; and that LIMKI expression may be associated with cancerous phenotype of the prostate.

Journal Title

Molecular Cancer

Volume

6

Publication Date

1-1-2007

Document Type

Article

Language

English

First Page

12

WOS Identifier

WOS:000248017600001

ISSN

1476-4598

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