PDLIM4, An Actin Binding Protein, Suppresses Prostate Cancer Cell Growth

We investigated the molecular function of PDLIM4 in prostate cancer cells. PDLIM4 mRNA and protein-expression levels were reduced in LNCaP, LAPC4, DU145, CWR22, and PC3 prostate cancer cells. The re-expression of PDLIM4 in prostate cancer cells has significantly reduced the cell growth and clonogenicity with G1 phase of cell-cycle arrest. We have shown the direct interaction of PDLIM4 with F-actin. Restoration of PDLIM4 expression resulted in reduction of tumor growth in xenografts. These results suggest that PDLIM4 may function as a tumor suppressor, involved in the control of cell proliferation by associating with actin in prostate cancer cells.

[1]  G. Gill,et al.  The PDZ domain of the LIM protein enigma binds to beta-tropomyosin. , 1999, Molecular biology of the cell.

[2]  E. Latulippe,et al.  Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease. , 2002, Cancer research.

[3]  E. Estey,et al.  RIL, a LIM gene on 5q31, is silenced by methylation in cancer and sensitizes cancer cells to apoptosis. , 2007, Cancer research.

[4]  C. Marshall,et al.  Activation of either ERK1/2 or ERK5 MAP kinase pathways can lead to disruption of the actin cytoskeleton , 2005, Journal of Cell Science.

[5]  J. Welsh,et al.  Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer. , 2001, Cancer research.

[6]  T. Vallenius,et al.  The PDZ-LIM protein RIL modulates actin stress fiber turnover and enhances the association of alpha-actinin with F-actin. , 2004, Experimental cell research.

[7]  Xiao-Feng Sun,et al.  Stromal staining for PINCH is an independent prognostic indicator in colorectal cancer. , 2004, Neoplasia.

[8]  Neil Sebire,et al.  A molecular map of mesenchymal tumors , 2005, Genome Biology.

[9]  Manqiu Cao,et al.  PCD1, a novel gene containing PDZ and LIM domains, is overexpressed in several human cancers. , 2000, Cancer research.

[10]  E. Tobias,et al.  The TES gene at 7q31.1 is methylated in tumours and encodes a novel growth-suppressing LIM domain protein , 2001, Oncogene.

[11]  R. Torella,et al.  Increased vascular endothelial growth factor mRNA expression in the heart of streptozotocin-induced diabetic rats. , 2003, Metabolism: clinical and experimental.

[12]  W. Lim,et al.  Rewiring cellular morphology pathways with synthetic guanine nucleotide exchange factors , 2007, Nature.

[13]  M. Becich,et al.  Gene expression alterations in prostate cancer predicting tumor aggression and preceding development of malignancy. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  M. Webber,et al.  Acinar Differentiation by Non-malignant Immortalized Human Prostatic Epithelial Cells and Its Loss by Malignant Cells Expression of the Basement Membrane Protein Laminin, Cell Adhesion Molecules Such as Cadherins and Integrin Receptors for Extracellular Matrix (ecm) Proteins. Normal Expression Of , 2022 .

[15]  G. W. Vuister,et al.  The interaction of PTP-BL PDZ domains with RIL: An enigmatic role for the RIL LIM domain , 2005, Molecular Biology Reports.

[16]  V. Speights,et al.  Gene Expression of Insulin-Like Growth Factors and Receptors in Neoplastic Prostate Tissues: Correlation with Clinico-pathological Parameters , 2001, Cancer investigation.

[17]  Michael M Lieber,et al.  PDLIM4 repression by hypermethylation as a potential biomarker for prostate cancer. , 2006, Clinical cancer research : an official journal of the American Association for Cancer Research.

[18]  J. Huot,et al.  Endothelial cell migration during angiogenesis. , 2007, Circulation research.

[19]  S. Inui,et al.  Cloning and Characterization of Androgen Receptor Coactivator, ARA55, in Human Prostate* , 1999, The Journal of Biological Chemistry.

[20]  R. Espinosa,et al.  Cytogenetic and molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[21]  S. Rhodes,et al.  LIM-homeodomain genes in mammalian development and human disease , 2005, Molecular Biology Reports.

[22]  R. Schüle,et al.  FHL2, a novel tissue‐specific coactivator of the androgen receptor , 2000, The EMBO journal.

[23]  J. Cheville,et al.  Transcriptional silencing of zinc finger protein 185 identified by expression profiling is associated with prostate cancer progression. , 2003, Cancer research.

[24]  W. Kolch,et al.  Oncogenic K-RAS is required to maintain changes in cytoskeletal organization, adhesion, and motility in colon cancer cells. , 2005, Cancer research.

[25]  M. Markelov,et al.  The human RIL gene: mapping to human chromosome 5q31.1, genomic organization and alternative transcripts. , 1998, Gene.

[26]  J. T. Corwin,et al.  Shape Change Controls Supporting Cell Proliferation in Lesioned Mammalian Balance Epithelium , 2007, The Journal of Neuroscience.

[27]  W. Kuo,et al.  Actinin-associated LIM Protein: Identification of a Domain Interaction between PDZ and Spectrin-like Repeat Motifs , 1997, The Journal of cell biology.

[28]  Olivier Cussenot,et al.  Extensive analysis of the 7q31 region in human prostate tumors supports TES as the best candidate tumor suppressor gene , 2004, International journal of cancer.

[29]  D. Chang,et al.  Inhibition of anchorage-independent growth of transformed NIH3T3 cells by epithelial protein lost in neoplasm (EPLIN) requires localization of EPLIN to actin cytoskeleton. , 2002, Molecular biology of the cell.

[30]  E. Cuppen,et al.  The zyxin-related protein TRIP6 interacts with PDZ motifs in the adaptor protein RIL and the protein tyrosine phosphatase PTP-BL. , 2000, European journal of cell biology.

[31]  C. Bagowski,et al.  PDZ and LIM Domain-Encoding Genes: Molecular Interactions and their Role in Development , 2007, TheScientificWorldJournal.

[32]  A. Chishti,et al.  Limatin (LIMAB1), an actin-binding LIM protein, maps to mouse chromosome 19 and human chromosome 10q25, a region frequently deleted in human cancers. , 1997, Genomics.

[33]  G. Gill,et al.  The PDZ Domain of the LIM Protein Enigma Binds to β-Tropomyosin , 1999 .

[34]  T. Vallenius,et al.  CLP-36 PDZ-LIM Protein Associates with Nonmuscle α-Actinin-1 and α-Actinin-4* , 2000, The Journal of Biological Chemistry.

[35]  Kohji Sato,et al.  The PDZ-LIM protein CLP36 is required for actin stress fiber formation and focal adhesion assembly in BeWo cells. , 2007, Biochemical and biophysical research communications.

[36]  T. Vallenius,et al.  Clik1: a novel kinase targeted to actin stress fibers by the CLP-36 PDZ-LIM protein. , 2002, Journal of cell science.

[37]  John T. Wei,et al.  Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression. , 2005, Cancer cell.

[38]  S. Dhanasekaran,et al.  Delineation of prognostic biomarkers in prostate cancer , 2001, Nature.

[39]  Tyson V. Sharp,et al.  LIM domains-containing protein 1 (LIMD1), a tumor suppressor encoded at chromosome 3p21.3, binds pRB and represses E2F-driven transcription. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[40]  P. Meltzer,et al.  Gene expression profiling of human sarcomas: insights into sarcoma biology. , 2005, Cancer research.