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Title: The FBXW7 {beta}-form is suppressed in human glioma cells

Abstract

FBXW7 (F-box and WD40 domain protein 7) is an F-box protein with 7 tandem WDs (tryptophan-aspartic acid) that functions as a phosphoepitope-specific substrate recognition component of SCF (Skp1-Cul1-F-box protein) ubiquitin ligases and catalyzes the ubiquitination of proteins promoting cell proliferation, such as CCNE1, MYC, AURKA, NOTCH1, and JUN, which are frequently activated in a wide range of human cancers. FBXW7 is a candidate tumor suppressor, and mutations have been reported in some human tumors. In this study, we analyzed 84 human tumor cell lines in search for genetic alterations of FBXW7, as well as mRNA and protein expressional changes, and compared them with expression levels of the CCNE1, MYC, and AURKA proteins. We found a novel nonsense mutation in a colon cancer cell line SCC and confirmed the missense mutations in SKOV3, an ovarian cancer cell line, and LoVo, a colon cancer cell line. Moreover, suppressed expression of FBXW7 accompanied by activation of the target proteins were observed in ovarian, colon, endometrial, gastric, and prostate cancers. It is notable that highly suppressed mRNA expression of the FBXW7 {beta}-form was found in all the human glioma cell lines analyzed; enhanced expressions of CCNE1, MYC, and AURKA were observed in these cells.more » Our present results imply that FBXW7 plays a pivotal role in many tissues by controlling the amount of cell cycle promoter proteins and that dysfunction of this protein is one of the essential steps in carcinogenesis in multiple organs.« less

Authors:
 [1];  [1];  [1];  [2]
  1. Department of Molecular Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575 (Japan)
  2. Department of Molecular Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575 (Japan). E-mail: horii@mail.tains.tohoku.ac.jp
Publication Date:
OSTI Identifier:
20979846
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 354; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2007.01.080; PII: S0006-291X(07)00126-X; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ASPARTIC ACID; CARCINOGENESIS; CELL CYCLE; CELL PROLIFERATION; GLIOMAS; HUMAN POPULATIONS; LARGE INTESTINE; LIGASES; MUTATIONS; PROSTATE; TRYPTOPHAN; TUMOR CELLS

Citation Formats

Gu, Zhaodi, Inomata, Kenichi, Ishizawa, Kota, and Horii, Akira. The FBXW7 {beta}-form is suppressed in human glioma cells. United States: N. p., 2007. Web. doi:10.1016/j.bbrc.2007.01.080.
Gu, Zhaodi, Inomata, Kenichi, Ishizawa, Kota, & Horii, Akira. The FBXW7 {beta}-form is suppressed in human glioma cells. United States. doi:10.1016/j.bbrc.2007.01.080.
Gu, Zhaodi, Inomata, Kenichi, Ishizawa, Kota, and Horii, Akira. Fri . "The FBXW7 {beta}-form is suppressed in human glioma cells". United States. doi:10.1016/j.bbrc.2007.01.080.
@article{osti_20979846,
title = {The FBXW7 {beta}-form is suppressed in human glioma cells},
author = {Gu, Zhaodi and Inomata, Kenichi and Ishizawa, Kota and Horii, Akira},
abstractNote = {FBXW7 (F-box and WD40 domain protein 7) is an F-box protein with 7 tandem WDs (tryptophan-aspartic acid) that functions as a phosphoepitope-specific substrate recognition component of SCF (Skp1-Cul1-F-box protein) ubiquitin ligases and catalyzes the ubiquitination of proteins promoting cell proliferation, such as CCNE1, MYC, AURKA, NOTCH1, and JUN, which are frequently activated in a wide range of human cancers. FBXW7 is a candidate tumor suppressor, and mutations have been reported in some human tumors. In this study, we analyzed 84 human tumor cell lines in search for genetic alterations of FBXW7, as well as mRNA and protein expressional changes, and compared them with expression levels of the CCNE1, MYC, and AURKA proteins. We found a novel nonsense mutation in a colon cancer cell line SCC and confirmed the missense mutations in SKOV3, an ovarian cancer cell line, and LoVo, a colon cancer cell line. Moreover, suppressed expression of FBXW7 accompanied by activation of the target proteins were observed in ovarian, colon, endometrial, gastric, and prostate cancers. It is notable that highly suppressed mRNA expression of the FBXW7 {beta}-form was found in all the human glioma cell lines analyzed; enhanced expressions of CCNE1, MYC, and AURKA were observed in these cells. Our present results imply that FBXW7 plays a pivotal role in many tissues by controlling the amount of cell cycle promoter proteins and that dysfunction of this protein is one of the essential steps in carcinogenesis in multiple organs.},
doi = {10.1016/j.bbrc.2007.01.080},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 354,
place = {United States},
year = {Fri Mar 23 00:00:00 EDT 2007},
month = {Fri Mar 23 00:00:00 EDT 2007}
}