Suppression of mammary-derived growth inhibitor gene expression by growth hormone and insulin-like growth factor I. 1998

H Huynh, and W Beamer
McGill University Centre for Translational Research in Cancer, Lady Davis Research Institute, Montreal, H3T 1E2 Quebec, Canada.

When introduced into MCF-7 breast cancer cells, the mammary-derived growth inhibitor (MDGI) gene causes them to revert to a more normal behavior. MDGI is silenced in several human breast cancer cell lines and in most breast tumors. Antiestrogens (tamoxifen and ICI 182780), which are commonly used in breast cancer treatment, stabilize MDGI mRNA. Insulin-like growth factors (IGFs) are well characterized mitogenic and anti-apoptotic factors involved in mammary gland physiology. We demonstrate that MDGI gene expression was inversely correlated with IGF-II gene expression. In the mammary gland of growth hormone releasing hormone receptor mutant (Ghrhrlit/Ghrhrlit) mice, the MDGI gene was overexpressed. Administration of IGF-I or GH to Ghrhrlit/Ghrhrlit mice suppressed MDGI mRNA levels in a dose-dependent manner. Administration of the somatostatin analogue octreotide to pituitary intact rats in a manner previously shown to acutely suppress the GH/IGF-I axis, up-regulated mammary gland MDGI expression in a dose-dependent fashion. The data document a previously unrecognized role of IGF-I in the regulation of the tumor suppressor gene MDGI, in the mammary gland, and may aid in the design of new physiological approaches to breast cancer prevention and/or treatment.

UI MeSH Term Description Entries
D007334 Insulin-Like Growth Factor I A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor. IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D007335 Insulin-Like Growth Factor II A well-characterized neutral peptide believed to be secreted by the LIVER and to circulate in the BLOOD. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on SOMATOTROPIN. It is believed to be a major fetal growth factor in contrast to INSULIN-LIKE GROWTH FACTOR I, which is a major growth factor in adults. IGF-II,Multiplication-Stimulating Activity,Somatomedin MSA,IGF-2,Insulin Like Growth Factor II,Insulin-Like Somatomedin Peptide II,Multiplication-Stimulating Factor,Somatomedin A,Factor, Multiplication-Stimulating,Insulin Like Somatomedin Peptide II,Multiplication Stimulating Activity,Multiplication Stimulating Factor
D008325 Mammary Neoplasms, Experimental Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS. Experimental Mammary Neoplasms,Neoplasms, Experimental Mammary,Experimental Mammary Neoplasm,Mammary Neoplasm, Experimental,Neoplasm, Experimental Mammary
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000074026 Fatty Acid Binding Protein 3 A small cytosolic fatty-acid binding protein that forms a lipid-binding beta-barrel structure and is expressed by CARDIOMYOCYTES and at lower levels in brain tissue. It is released into plasma immediately following cardiac injury and may therefore serve as a useful biomarker for the early detection of MYOCARDIAL INFARCTION. H-FABP,Heart Fatty Acid Binding Protein,Heart-Specific Fatty Acid Binding Protein,Muscle Fatty Acid-Binding Protein,Heart Specific Fatty Acid Binding Protein,Muscle Fatty Acid Binding Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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