The overall objectives of this project are to better define the molecular mechanisms by which polypeptide growth factors can modulate proliferation of nontumorigenic mammalian cells and to define how tumorigenic cells escape from normal growth control. The unifying hypotheses upon which the experiments in this project are predicated are as follows. First, the proliferation of mammalian cells in vitro and in vivo can be controlled by the action of polypeptide growth factors. Second, inappropriate production of polypeptide growth factors by transformed cells can lead to uncontrolled growth (autocrine stimulation). Third, transformed cells may produce multiple factors that are responsible for invasion and proliferation of stromal elements (including endothelial cells) into solid tumors. One growth factor which has not been widely studied in this regard is fibroblast growth factor (FGF). Therefore, the specific aims of this project include: (1) Expanded studies on the isolation of purified FGF from bovine pituitary glands. This will include amino acid analysis and N-terminal sequencing. (2) Continued studies on the interaction of purified FGF with other growth factors and hormones in stimulating proliferation of nontransformed cells in a defined (serum-free) media. (3) Development of a radioassay for FGF binding to target cells to determine the number and affinity of the putative FGF receptor. (4) Examination of the conditioned medium from various tumor cells to determine whether transformed cells produce FGF-like molecules. (J)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA042409-02
Application #
3183679
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1985-08-01
Project End
1987-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Cook, P W; Ashton, N M; Karkaria, C E et al. (1995) Differential effects of a heparin antagonist (hexadimethrine) or chlorate on amphiregulin, basic fibroblast growth factor, and heparin-binding EGF-like growth factor activity. J Cell Physiol 163:418-29
Pittelkow, M R; Cook, P W; Shipley, G D et al. (1993) Autonomous growth of human keratinocytes requires epidermal growth factor receptor occupancy. Cell Growth Differ 4:513-21
Li, S; Plowman, G D; Buckley, S D et al. (1992) Heparin inhibition of autonomous growth implicates amphiregulin as an autocrine growth factor for normal human mammary epithelial cells. J Cell Physiol 153:103-11
Cook, P W; Pittelkow, M R; Keeble, W W et al. (1992) Amphiregulin messenger RNA is elevated in psoriatic epidermis and gastrointestinal carcinomas. Cancer Res 52:3224-7
Cook, P W; Mattox, P A; Keeble, W W et al. (1992) Inhibition of autonomous human keratinocyte proliferation and amphiregulin mitogenic activity by sulfated polysaccharides. In Vitro Cell Dev Biol 28A:218-22
Eckenstein, F P; Shipley, G D; Nishi, R (1991) Acidic and basic fibroblast growth factors in the nervous system: distribution and differential alteration of levels after injury of central versus peripheral nerve. J Neurosci 11:412-9
Cook, P W; Mattox, P A; Keeble, W W et al. (1991) A heparin sulfate-regulated human keratinocyte autocrine factor is similar or identical to amphiregulin. Mol Cell Biol 11:2547-57
Root, L L; Shipley, G D (1991) Human dermal fibroblasts express multiple bFGF and aFGF proteins. In Vitro Cell Dev Biol 27A:815-22
Cook, P W; Pittelkow, M R; Shipley, G D (1991) Growth factor-independent proliferation of normal human neonatal keratinocytes: production of autocrine- and paracrine-acting mitogenic factors. J Cell Physiol 146:277-89
Li, S; Shipley, G D (1991) Expression of multiple species of basic fibroblast growth factor mRNA and protein in normal and tumor-derived mammary epithelial cells in culture. Cell Growth Differ 2:195-202

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