Differential expression analysis of MIM (MTSS1) splice variants and a functional role of MIM in prostate cancer cell biology

Int J Oncol. 2005 Jun;26(6):1699-705.

Abstract

We previously identified MIM-A (missing in metastasis, MTSS1) by differential display techniques as missing in invasive, metastatic bladder cancer cell lines and suggested that MIM-A is a novel putative metastasis suppressor gene. Characterization of the MIM gene revealed a WH2 (Wiskott-Aldrich syndrome protein homology 2) domain in the C-terminus that is known to bind actin monomers and regulate organization of the actin cytoskeleton. Here, we further describe two alternatively splice variants of MIM-A, called MIM(12del) and MIM-B, which share > 50% amino acid sequence homology with MIM-A in the C-terminal domain. We show that expression of all three transcripts is down-regulated in prostate cancer cell lines and tumor samples from patients. In addition, we generated stably-transfected PC-3 cells overexpressing MIM-A to evaluate the importance of MIM-A in prostate cancer biology. The initial experiments show that expression of MIM decreased the number of actin filaments and was associated with a decrease in the G:F actin ratio. Overexpression of MIM-A had no effect on PC-3 cell adhesion to extracellular matrices, as well as no effect on PC-3 motility. Further, overexpression of MIM-A reduced the rate of PC-3 cell proliferation. These results support the hypothesis that MIM-A is an actin-binding protein and implicate a role of MIM-A in the regulation of cellular proliferation. These data suggest that the reduction of MIM-A gene expression in prostate cancer and other cancers may contribute to tumor growth and development, as well as metastasis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Alternative Splicing
  • Cell Proliferation
  • Gene Expression Regulation
  • Humans
  • Male
  • Microfilament Proteins / genetics
  • Microfilament Proteins / physiology*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*

Substances

  • Actins
  • MTSS1 protein, human
  • Microfilament Proteins
  • Neoplasm Proteins