INSULIN-LIKE GROWTH FACTOR-I PRODUCTION AND RECEPTORS IN MAMMARY ADENOCARCINOMAS INDUCED BY MEDROXYPROGESTERONE ACETATE IN BALB/C MICE

The production of insulin-like growth factor-I (IGF-I) and the presence of IGF-I receptors (IGF-I-R) were examined in three hormone-dependent (MPA-D) and two hormone-independent (MPA-I) tumor lines of mammary adenocarcinomas induced by medroxy progesterone acetate (MPA) in BALB/c mice. Immunoreactive IGF-I was detected in acid-ethanol extracts from all MPA-D and MPA-I tumors. To avoid interferences in the IGF-I radioimmunoassay (RIA) by IGF binding proteins (IGF-BPs), acid extracts of tumor samples were purified by Sep-Pack C18 chromatography. Similar levels of IGF-I were detected by the two methods. No induction of IGF-I synthesis by MPA was observed and IGF-I production in MPA-D and MPA-I lines was similar. The presence of an IGF-BP of an apparent Mr of 43 kDa was detected in MPA-D and MPA-I tumors. Specific IGF-I binding was demonstrated in hormone-dependent and unresponsive tumors and the levels of IGF-I receptors were not regulated by MPA, being similar in MPA-D and MPA-I tumors. Scatchard analysis of the binding data showed the presence of high (Kd = 3.4x10(-12) M, Q = 22.5 fmol/mg protein) and low affinity (Kd = 1.3x10(-10) M, Q = 143.7 fmol/mg protein) binding sites. Chemical cross-linking of I-125-IGF to the membranes of MPA-D and MPA-I tumors showed two labeled bands in the Mr regions corresponding to type I (130 KDa) and II (260 KDa) IGFs receptors. The results suggest that IGF-I plays an autocrine/paracrine role in the vivo breast tumor growth.