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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}
}
  • Highlights: • RITA overexpression increased protein expression of p53 and Fbxw7 and downregulated the expression of cyclin D1, cyclin E, CDK2, Hes-1 and NF-κB p65. • RITA can significantly inhibit the in vitro growth of SMMC7721 and HepG2 cells. • RITA exerts tumor-suppressive effects in hepatocarcinogenesis through induction of G0/G1 cell cycle arrest and apoptosis and suggest a therapeutic application of RITA in HCC. - Abstract: Aberrant Notch signaling is observed in human hepatocellular carcinoma (HCC) and has been associated with the modulation of cell growth. However, the role of Notch signaling in HCC and its underlying mechanism remain elusive.more » RBP-J-interacting and tubulin-associated (RITA) mediates the nuclear export of RBP-J to tubulin fibers and downregulates Notch-mediated transcription. In this study, we found that RITA overexpression increased protein expression of p53 and Fbxw7 and downregulated the expression of cyclin D1, cyclin E, CDK2, Hes-1 and NF-κB p65. These changes led to growth inhibition and induced G0/G1 cell cycle arrest and apoptosis in SMMC7721 and HepG2 cells. Our findings indicate that RITA exerts tumor-suppressive effects in hepatocarcinogenesis through induction of G0/G1 cell cycle arrest and apoptosis and suggest a therapeutic application of RITA in HCC.« less
  • DNA polymerase inactivation is compared to thermal radiosensitization and inhibition of damage recovery in human glioma cells. Two human glioma cell lines (U87MG and U373MG) were exposed to hyperthermia and irradiation. Hyperthermia was given at 43[degrees]C and 45[degrees]C and DNA polymerase [alpha] + [delta] + [epsilon] and [beta] activities were measured. Hyperthermia was given at various times before irradiation and the degree of radiosensitization and polymerase activity was assessed at various times after heating. In addition the ability of cells to undergo repair of potentially lethal radiation damage was assessed for cells irradiated at various times after heating. Polymerase [alpha]more » + [delta] + [epsilon] and polymerase [beta] both recovered after heating but polymerase [beta] was faster and was complete in U373MG but not in the U87MG cell lines after 48 h incubation after heating (45[degrees]C, 60 min). Incubation, between hyperthermia and irradiation resulted in a loss of radiosensitization and a loss of inhibition of repair of potentially lethal damage. These changes correlated well with recovery of polymerase [beta] but not with polymerase [alpha] + [delta] + [epsilon]. The correlation of polymerase [beta] activity and thermoradiosensitization and its recovery indicate that polymerase [beta] may be one of the mechanisms involved in thermoradiosensitization. 35 refs., 7 figs.« less
  • This in vitro study was undertaken to determine if ultrahigh dose rates could improve the radiation response of human tumors. Two cell lines, human glioma (U-87 MG), which is radioresistant, and human melanoma (HT-144), which is radiosensitive, were irradiated at ultrahigh and high dose rates under aerobic and anoxic conditions to determine if their oxygen enhancement ratios are modified by dose rate. In fact, the survival curves, and hence the oxygen enhancement ratios, were found to be independent of the dose rate. The oxygen enhancement ratio for glioma cells irradiated in plateau phase was 2.8 ({+-} 0.3). The oxygen enhancementmore » ratio was 2.7 ({+-} 0.4) for melanoma cells in plateau phase and 2.8 ({+-} 0.3) in exponential phase. These results indicate that there is no advantage in treating these tumors using ultrahigh dose rate instead of conventional dose rates. 28 refs., 4 figs., 1 tab.« less
  • In this study the kinetics of recovery following irradiation was examined in a human glioma cell line. Specific objectives were: to determine whether recovery is mono- or biexponential in nature; to determine if recovery half-times are different in exponential and plateau growth phase cells; to compare recovery half-times as a function of dose or recovery levels; and finally, to compare the kinetics of sublethal damage recovery and potentially lethal damage recovery in plateau growth phase cells. U-87MG cells were irradiated in exponential and plateau growth phases and then subjected to incubation at 37{degrees}C for various periods of time following ormore » between doses prior to assaying for survival. Survival recovery curves were fit to a sum of exponential terms. Potentially lethal damage recovery was monoexponential in both exponential and plateau growth phase cells and occurred at the same rate when isorecovery values were compared. Recovery half-times increased in an exponential manner within the observed dose range. Recovery between doses of radiation (sublethal damage recovery) proceeded at a slower rate than recovery following a single dose of radiation (potentially lethal damage recovery). This study suggests that potentially lethal damage recovery is a saturated process and that the recovery half-time may increase in a linear-quadratic exponential function of dose similar to the absolute recovery level. In addition, if iso-recovery levels are compared, the recovery half-time is similar in rapidly and slowly proliferating cell populations. 42 refs., 6 figs., 3 tabs.« less