AUTOCRINE TRANSFORMING GROWTH FACTOR-BETA(1) AND BETA(2) EXPRESSION IS INCREASED BY CELL CROWDING AND QUIESCENCE IN COLON-CARCINOMA CELLS

被引:30
作者
SUN, LZ
WU, SP
COLEMAN, K
FIELDS, KC
HUMPHREY, LE
BRATTAIN, MG
机构
[1] MED COLL OHIO,DEPT BIOCHEM & MOLEC BIOL,TOLEDO,OH 43699
[2] BAYLOR COLL MED,DEPT PHARMACOL,HOUSTON,TX 77030
[3] BRISTOL MYERS SQUIBB CO,DEPT MOLEC GENET,PRINCETON,NJ 08543
关键词
D O I
10.1006/excr.1994.1251
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Although a great deal is known about the cellular effects of exogenous transforming growth factor-beta (TGF-beta) treatment and the effects of various exogenous agents (including TGF-beta's themselves) on TGF-beta expression, studies of cellular controls for autocrine TGF-beta expression and function have been rare. Since exogenous TGF-beta treatment blocks progression through the cell cycle, it seemed likely that autocrine TGF-beta activity would be induced by growth states in which there was little or no cell division such as confluency or quiescence. Specific TGF-beta(1) or beta(2) neutralizing antibody treatment of a colon carcinoma cell line designated CBS showed that autocrine TGF-beta activity could be demonstrated in quiescent cells but not in preconfluent cells. Studies of kinetics of TGF-beta(1) and beta(2) mRNA levels during the establishment of quiescence revealed a significant increase of both isoforms in quiescent cells. The quiescent cells also secreted three- to fourfold and four-to fivefold higher levels of total (latent plus active) TGF-beta(1) and beta(2) protein in the conditioned media than the confluent cells and preconfluent cells, respectively. There was no detectable active form of either TGF-beta isoform in the conditioned media of preconfluent cells, whereas a significant amount of active TGF-beta(1) and beta(2) was detected in the conditioned media of quiescent cells, Quantitative RNase protection assays were developed to compare the effects of cell crowding vs quiescence on TGF-beta expression. TGF-beta(1) was primarily induced by quiescence. TGF-beta(2) was induced by both quiescence and cell crowding. Increased TGF-beta(1) mRNA levels appeared to be exclusively due to an increase in stability, while increased TGF-beta(2) mRNA levels were due to increased transcription. This growth state-related induction of TGF-beta's was also observed in two other colon carcinoma cell lines. These studies show that TGF-beta(1) and beta(2) are autocrine-negative factors which can be situationally expressed by cells as a function of their growth state. Autocrine expression of the TGF-beta's in this model system appears not to affect exponentially growing cells, but rather to function by maintaining a quiescent state and/or by blocking progression through the cell cycle. (C) 1994 Academic Press, Inc.
引用
收藏
页码:215 / 224
页数:10
相关论文
共 44 条
[1]  
ARTEAGA CL, 1990, CELL GROWTH DIFFER, V1, P367
[2]   COMPLEX REGULATION OF TRANSFORMING GROWTH FACTOR-BETA-1, FACTOR-BETA-2, AND FACTOR-BETA-3 MESSENGER-RNA EXPRESSION IN MOUSE FIBROBLASTS AND KERATINOCYTES BY TRANSFORMING GROWTH FACTOR-BETA-1 AND FACTOR-BETA-2 [J].
BASCOM, CC ;
WOLFSHOHL, JR ;
COFFEY, RJ ;
MADISEN, L ;
WEBB, NR ;
PURCHIO, AR ;
DERYNCK, R ;
MOSES, HL .
MOLECULAR AND CELLULAR BIOLOGY, 1989, 9 (12) :5508-5515
[3]  
BRATTAIN MG, 1981, ONCODEV BIOL MED, V2, P355
[4]   THE RETINOBLASTOMA PROTEIN IS PHOSPHORYLATED DURING SPECIFIC PHASES OF THE CELL-CYCLE [J].
BUCHKOVICH, K ;
DUFFY, LA ;
HARLOW, E .
CELL, 1989, 58 (06) :1097-1105
[5]   PHOSPHORYLATION OF THE RETINOBLASTOMA GENE-PRODUCT IS MODULATED DURING THE CELL-CYCLE AND CELLULAR-DIFFERENTIATION [J].
CHEN, PL ;
SCULLY, P ;
SHEW, JY ;
WANG, JYJ ;
LEE, WH .
CELL, 1989, 58 (06) :1193-1198
[6]   ISOLATION OF BIOLOGICALLY-ACTIVE RIBONUCLEIC-ACID FROM SOURCES ENRICHED IN RIBONUCLEASE [J].
CHIRGWIN, JM ;
PRZYBYLA, AE ;
MACDONALD, RJ ;
RUTTER, WJ .
BIOCHEMISTRY, 1979, 18 (24) :5294-5299
[7]   THE MYC ONCOGENE - ITS ROLE IN TRANSFORMATION AND DIFFERENTIATION [J].
COLE, MD .
ANNUAL REVIEW OF GENETICS, 1986, 20 :361-384
[8]   THE PRODUCT OF THE RETINOBLASTOMA SUSCEPTIBILITY GENE HAS PROPERTIES OF A CELL-CYCLE REGULATORY ELEMENT [J].
DECAPRIO, JA ;
LUDLOW, JW ;
LYNCH, D ;
FURUKAWA, Y ;
GRIFFIN, J ;
PIWNICAWORMS, H ;
HUANG, CM ;
LIVINGSTON, DM .
CELL, 1989, 58 (06) :1085-1095
[9]   EXPRESSION AND STATE OF PHOSPHORYLATION OF THE RETINOBLASTOMA SUSCEPTIBILITY GENE-PRODUCT IN CYCLING AND NONCYCLING HUMAN HEMATOPOIETIC-CELLS [J].
FURUKAWA, Y ;
DECAPRIO, JA ;
FREEDMAN, A ;
KANAKURA, Y ;
NAKAMURA, M ;
ERNST, TJ ;
LIVINGSTON, DM ;
GRIFFIN, JD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (07) :2770-2774
[10]   INDUCTION AND AUTOCRINE RECEPTOR-BINDING OF TRANSFORMING GROWTH FACTOR-BETA-2 DURING TERMINAL DIFFERENTIATION OF PRIMARY MOUSE KERATINOCYTES [J].
GLICK, AB ;
DANIELPOUR, D ;
MORGAN, D ;
SPORN, MB ;
YUSPA, SH .
MOLECULAR ENDOCRINOLOGY, 1990, 4 (01) :46-52