Transforming properties of a Q18-->E mutation of the microtubule regulator Op18.
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.
Misek
David E
DE
Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA. d.misek@umich.edu
Chang
Christina L
CL
Kuick
Rork
R
Hinderer
Robert
R
Giordano
Thomas J
TJ
Beer
David G
DG
Hanash
Samir M
SM
D016475:3T3 Cells; D000230:Adenocarcinoma / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional; D004938:Esophageal Neoplasms / Q000235:genetics; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D008868:Microtubule Proteins; D008870:Microtubules / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D017354:Point Mutation / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050777:Stathmin; D014404:Tubulin / Q000378:metabolism / Q000648:ultrastructure
D008868:Microtubule Proteins; D010750:Phosphoproteins; C493995:STMN1 protein, human; D050777:Stathmin; C493994:Stmn1 protein, mouse; D014404:Tubulin