Transforming Properties of a Q18-->E Mutation of the Microtubule Regulator Op18

Cancer Cell. 2002 Sep;2(3):217-28. doi: 10.1016/s1535-6108(02)00124-1.

Abstract

We have identified a somatic mutation in Op18 in a human esophageal adenocarcinoma. The mutant form of Op18 (M-Op18) was cloned and sequenced, revealing a substitution of a G for C at nucleotide 155, which results in a Q18-->E substitution in the protein. M-Op18 cDNA was expressed in NIH/3T3 cells, which resulted in foci formation and tumor growth in immunodeficient mice. Cell cycle analysis of M-Op18-expressing cells revealed a doubling in the percentage of cells in G2/M relative to cells overexpressing wild-type Op18, a decrease in M-Op18-specific phosphorylation, and alterations in tubulin ultrastructure in M-Op18-expressing cells. These results suggest that the somatic mutation identified in Op18 has profound effects on cell homeostasis that may lead to tumorigenicity.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Adenocarcinoma / genetics
  • Animals
  • Blotting, Western
  • Cell Division / genetics
  • Cell Transformation, Neoplastic / genetics*
  • Electrophoresis, Gel, Two-Dimensional
  • Esophageal Neoplasms / genetics
  • Fluorescent Antibody Technique
  • Humans
  • Mice
  • Microtubule Proteins*
  • Microtubules / genetics
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Point Mutation / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stathmin
  • Tubulin / metabolism
  • Tubulin / ultrastructure

Substances

  • Microtubule Proteins
  • Phosphoproteins
  • STMN1 protein, human
  • Stathmin
  • Stmn1 protein, mouse
  • Tubulin