Regulation of insulin-like growth factors by antiestrogen. 1994

R Winston, and P C Kao, and D T Kiang
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.

Insulin-like growth factors are potent mitogens for breast cancer cell proliferation. This effect is modulated by the circulatory and extracellular IGFBPs as well as by the affinity of ligand binding receptors on the target cells. Antiestrogens have been shown to reduce both circulatory and microenvironmental IGF levels and thus suppress the IGF-I-induced growth of both ER-positive and ER-negative breast cancer cells. However, the effects of antiestrogens in down regulation of type I IGF receptor and in altering the autophosphorylation tyrosine kinase activity of EGF receptors are mainly observed in ER-positive cells. Furthermore, alteration of IGFBP by antiestrogens such as a marked increase of IGFBP-I production have been shown to inhibit the proliferative effect of IGF-I on ER-positive, but stimulate this effect, on ER-negative cells. Such differential effects from IGF receptor and IGFBP may explain the clinical outcome that tumor regression from antiestrogens is mainly observed in ER-positive type. This assumption based on IGF regulation alone is certainly an oversimplistic view amid the complexity of autocrine, paracrine, and endocrine functions.

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
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D011960 Receptors, Estrogen Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important. Estrogen Receptor,Estrogen Receptors,Estrogen Nuclear Receptor,Estrogen Receptor Type I,Estrogen Receptor Type II,Estrogen Receptors Type I,Estrogen Receptors Type II,Receptor, Estrogen Nuclear,Receptors, Estrogen, Type I,Receptors, Estrogen, Type II,Nuclear Receptor, Estrogen,Receptor, Estrogen
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
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
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D004965 Estrogen Antagonists Compounds which inhibit or antagonize the action or biosynthesis of estrogenic compounds. Estradiol Antagonists,Antagonists, Estradiol,Antagonists, Estrogen
D005260 Female Females
D006131 Growth Inhibitors Endogenous or exogenous substances which inhibit the normal growth of human and animal cells or micro-organisms, as distinguished from those affecting plant growth ( Cell Growth Inhibitor,Cell Growth Inhibitors,Growth Inhibitor,Growth Inhibitor, Cell,Growth Inhibitors, Cell,Inhibitor, Cell Growth,Inhibitor, Growth,Inhibitors, Cell Growth,Inhibitors, Growth
D006133 Growth Substances Signal molecules that are involved in the control of cell growth and differentiation. Mitogens, Endogenous,Endogenous Mitogens

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