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

    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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