Regulation of vascular endothelial growth factor expression in human colon carcinoma cells by activity of src kinase

被引:40
作者
Fleming, RYD
Ellis, LM
Parikh, NU
Liu, WB
Staley, CA
Gallick, GE
机构
[1] UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT TUMOR BIOL,HOUSTON,TX 77030
[2] UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT SURG ONCOL,HOUSTON,TX 77030
[3] UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT CELL BIOL,HOUSTON,TX 77030
[4] EMORY UNIV,SCH MED,DEPT SURG ONCOL,ATLANTA,GA
关键词
D O I
10.1016/S0039-6060(97)90044-1
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background. The c-src protooncogene encodes a protein tyrosine Kinase, pp60(c-src), that is a mediator in many signal transduction pathways. One pathway in which pp60(c-src) protein tyrosine kinase activity is implicated involves regulation of vascular endothelial growth factor (VEGF) an angiogenic factor important to neovascularization of growing tumors. Recently we demonstrated that decreased activity of pp60(c-src) in colon tumor cells contributes to decreased expression of VEGF. This study examined the relationship between pp60(C-src) activation cell density, and VEGF production in a colon tumor cell line. Methods. Parental HT-29 colon adenocarcinoma cells and stable subclones created by transfection with c-src antisense and sense (control) expression vectors were plated under sparse (2 x 10(4) cells/cm(2)) and confluent (20 x 10(4) cells/cm(2)) conditions and grown for 36 hours. Protein and RNA were extracted from cells to determine pp60(c-src) levels c-Src tyrosine kinase activity, and VEGF mRNA expression. Results. The pp60(c-src) kinase activity of HT-29 cells and control sense-transfected clones grown under confluent conditions was increased threefold to fivefold compared with cells grown under sparse conditions. In contrast, the ability of confluent culture conditions to increase pp60(c-src) activity was blunted in antisense transfectants. By regression analysis, VEGF expression was found to vary directly with pp60-(c) (src) levels (r(2) = 0. 886). Conclusions. Cell density contributes to the regulation of c-src kinase activity and VEGF expression in HT-29 cells. When the steady-state level of pp60(c-src) is reduced in antisense transfectants, not only is the steady-state level of VEGF reduced, but the ability of confluence to stimulate pp60(c-src) activity and VEGF production is too. These data suggest that c-src may be an intermediary of both constitutive and I inducible pathways for VEGF production in colon tumor cells.
引用
收藏
页码:501 / 507
页数:7
相关论文
共 20 条
[1]   ACTIVATION OF PP60C-SRC PROTEIN-KINASE ACTIVITY IN HUMAN-COLON CARCINOMA [J].
BOLEN, JB ;
VEILLETTE, A ;
SCHWARTZ, AM ;
DESEAU, V ;
ROSEN, N .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (08) :2251-2255
[2]  
BROWN LF, 1993, AM J PATHOL, V143, P1255
[3]  
BROWN LF, 1993, CANCER RES, V53, P4727
[4]   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
[5]   ALTERED PHOSPHORYLATION AND ACTIVATION OF PP60C-SRC DURING FIBROBLAST MITOSIS [J].
CHACKALAPARAMPIL, I ;
SHALLOWAY, D .
CELL, 1988, 52 (06) :801-810
[6]   Down-regulation of vascular endothelial growth factor in hunan colon carcinoma cell lines by antisense transfection decreases endothelial cell proliferation [J].
Ellis, LM ;
Liu, WB ;
Wilson, M .
SURGERY, 1996, 120 (05) :871-878
[7]   THE IMPLICATIONS OF ANGIOGENESIS FOR THE BIOLOGY AND THERAPY OF CANCER METASTASIS [J].
FIDLER, IJ ;
ELLIS, LM .
CELL, 1994, 79 (02) :185-188
[8]  
Fogh J., 1975, HUMAN TUMOR CELLS IN, P115, DOI DOI 10.1007/978-1-4757-1647-4_5
[9]   Overexpression of focal adhesion kinase (p125(FAK)) in human colorectal carcinoma liver metastases: Independence from c-src or c-yes activation [J].
Han, NM ;
Fleming, RYD ;
Curley, SA ;
Gallick, GE .
ANNALS OF SURGICAL ONCOLOGY, 1997, 4 (03) :264-268
[10]  
Koura AN, 1996, CANCER RES, V56, P3891