Expression of insulin-like growth factor I, its binding proteins, and its receptor in ovarian cancer.
Insulin-like growth factor (IGF) I is a polypeptide hormone important in normal growth and development. Although IGF-I is a mitogen for many cancer cell lines, previous work has suggested that autocrine production of IGF-I is uncommon in cancers of epithelial origin. In this study, expression of IGF-I, its binding proteins, and its receptor were examined in ovarian cancer cell lines and tissues. Of 10 ovarian cancer cell lines, 3 (OVCAR-3, OVCAR-7, and PEO4) expressed IGF-I mRNA. RNase protection assays using probes derived from IGF-IA, IGF-IB, and alternate exon 1 IGF-I complementary DNAs demonstrated that these cells contained a predominant IGF-I transcript with an alternate first exon. RNA extracted from primary and metastatic ovarian cancer tissues also expressed IGF-I mRNAs (7 of 7) with the alternate first exon. IGF-I protein was detected in OVCAR-3-conditioned media; this activity was secreted in conjunction with several IGF-binding proteins (IGFBPs). IGFBP-2, IGFBP-3, an Mr 24,000 species, and an Mr 30,000 species could also be demonstrated in OVCAR-3. Type I IGF receptor mRNA was found in all 10 of the ovarian cancer cell lines and all 7 of the primary or metastatic ovarian cancer tissues. IGF-I was a mitogen for OVCAR-3, demonstrating the presence of a functional type I IGF receptor. These data show that all the necessary components for an IGF-I-mediated autocrine loop are expressed by ovarian cancer cells.
Yee
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Division of Medical Oncology, University of Texas Health Science Center, San Antonio 78284.
Morales
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Hamilton
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Von Hoff
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D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015342:DNA Probes; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D012313:RNA / Q000096:biosynthesis; D011863:Radioimmunoassay; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D015342:DNA Probes; D018969:Insulin-Like Growth Factor Binding Proteins; D012313:RNA; D007334:Insulin-Like Growth Factor I