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- Title
The Insulin-Like Growth Factor Type I Receptor Stimulates Growth and Suppresses Apoptosis in Prostatic Stromal Cells.
- Authors
GRANT, EWAN S.; ROSS, MARGARET B.; BALLARD, STEPHEN; NAYLOR, ALASDAIR; HABIB, FOUAD K.
- Abstract
Stromal cells derived from benign prostatic hyperplasia synthesize and secrete measurable levels of insulin-like growth factor (IGF). Seventy-two-hour conditioned medium obtained from these cells contains IGF-II at levels ranging from 125–177 ng/mL·106 cells. IGF-I is almost undetectable. RT-PCR analysis has demonstrated that the genes for both the type I IGF receptor (IGF-IR) and the type II IGF receptor (IGF-IIR) are expressed by benign stromal cells in vitro. Competition binding analysis for IGF-I and IGF-II confirmed the existence of binding sites for both ligands with respective Kd and binding capacities of 4.9 × 10−9 mol/L and 6.6 × 105 sites/cell and 4.7 × 10−9 mol/L and 3.8 × 106 sites/cell. Under serum-free conditions, IGF-I and IGF-II at 500 ng/mL induce 80% and 113% increases in stromal cell density, respectively, over a 96-h period. Incubation with the IGF-IR-neutralizing antibodyα IR3 (50 μg/mL) reduces the rate of stromal cell proliferation by approximately 60–80% even in the presence of stimulatory concentrations of IGFs. Camptothecin-induced apoptosis is inhibited by the addition of IGF-I and -II (500 ng/mL). αIR3 suppresses these survival signals and itself induces cell death in the prostatic stroma. The data suggest that IGF-IR is a pivotal molecule in prostatic stromal cell maintenance, and that specific antagonism may offer a novel means of controlling the fibromuscular expansion characteristic of benign prostatic hyperplasia.
- Publication
Journal of Clinical Endocrinology & Metabolism, 1998, Vol 83, Issue 9, p3252
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/jcem.83.9.5119