SRC transcriptional activation in a subset of human colon cancer cell lines

被引:43
作者
Dehm, S
Senger, MA
Bonham, K [1 ]
机构
[1] Saskatchewan Canc Agcy, Hlth Res Div, Canc Res Unit, Saskatoon, SK S7N 4H4, Canada
[2] Univ Saskatchewan, Dept Biochem, Saskatoon, SK S7N 5E5, Canada
[3] Univ Saskatchewan, Div Oncol, Saskatoon, SK S7N 4H4, Canada
基金
英国医学研究理事会;
关键词
c-Src; oncogene activation; transcription; colon cancer;
D O I
10.1016/S0014-5793(00)02354-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human SRC encodes the non-receptor tyrosine kinase pp60(c-Src), which is activated in many human colon cancer cell lines (HCCLs) and tumors. We found that both c-Src protein and mRNA levels were elevated in a subset of HCCLs. Increased c-Src mRNA and protein levels correlated strongly with increased c-Src kinase activity. Nuclear run-on analysis and c-Src mRNA half-life determination demonstrated increased mRNA levels were due to increased transcription of the SRC gene. We also observed decreased c-Src mRNA stability in cell lines that displayed SRC transcriptional activation. Our findings provide the first evidence that SRC transcriptional activation is an important determinant of c-Src expression and activity in HCCLs. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:367 / 371
页数:5
相关论文
共 41 条
[11]   PP60C-SRC ACTIVATION IN HUMAN-COLON CARCINOMA [J].
CARTWRIGHT, CA ;
KAMPS, MP ;
MEISLER, AI ;
PIPAS, JM ;
ECKHART, W .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (06) :2025-2033
[12]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[13]   Down-regulation of vascular endothelial growth factor in a human colon carcinoma cell line transfected with an antisense expression vector specific for c-src [J].
Ellis, LM ;
Staley, CA ;
Liu, WB ;
Fleming, RYD ;
Parikh, NU ;
Bucana, CD ;
Gallick, GE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (02) :1052-1057
[14]   A GENETIC MODEL FOR COLORECTAL TUMORIGENESIS [J].
FEARON, ER ;
VOGELSTEIN, B .
CELL, 1990, 61 (05) :759-767
[15]  
FEI HH, 1993, BIOTECHNIQUES, V15, P838
[16]   Ubiquitin-dependent degradation of active Src [J].
Hakak, Y ;
Martin, GS .
CURRENT BIOLOGY, 1999, 9 (18) :1039-1042
[17]   Ubiquitin-mediated degradation of active Src tyrosine kinase [J].
Harris, KF ;
Shoji, I ;
Cooper, EM ;
Kumar, S ;
Oda, H ;
Howley, PM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (24) :13738-13743
[18]  
Iravani S, 1998, LAB INVEST, V78, P365
[19]   Activating SRC mutation in a subset of advanced human colon cancers [J].
Irby, RB ;
Mao, WG ;
Coppola, D ;
Kang, J ;
Loubeau, JM ;
Trudeau, W ;
Karl, R ;
Fujita, DJ ;
Jove, R ;
Yeatman, TJ .
NATURE GENETICS, 1999, 21 (02) :187-190
[20]   Inhibition of pp60c-Src reduces Bcl-XL expression and reverses the transformed phenotype of cells overexpressing EGF and HER-2 receptors [J].
Karni, R ;
Jove, R ;
Levitzki, A .
ONCOGENE, 1999, 18 (33) :4654-4662