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Role of insulin‐like growth factor binding protein‐3 in breast cancer cell growth
Author(s) -
Schedlich Lynette J.,
Graham Lloyd D.
Publication year - 2002
Publication title -
microscopy research and technique
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 118
eISSN - 1097-0029
pISSN - 1059-910X
DOI - 10.1002/jemt.10173
Subject(s) - growth factor , cell growth , biology , microbiology and biotechnology , insulin like growth factor binding protein , insulin like growth factor , signal transduction , receptor , growth factor receptor inhibitor , cell cycle , intracellular , cell surface receptor , endocrinology , medicine , cell , growth factor receptor , biochemistry
The mitogenic effects of insulin‐like growth factors (IGFs) are regulated by a family of insulin‐like growth factor binding proteins (IGFBPs). One member of this family, IGFBP‐3, mediates the growth‐inhibitory and apoptosis‐inducing effects of a number of growth factors and hormones such as transforming growth factor‐β, retinoic acid, and 1,25‐dihydroxyvitamin D 3 . IGFBP‐3 may act in an IGF‐dependent manner by attenuating the interaction of pericellular IGFs with the type‐I IGF receptor. It may also act in an IGF‐independent manner by initiating intracellular signaling from a cell surface receptor, or by direct nuclear action, or both. The possibility of a membrane‐bound receptor is strengthened by recent studies which have identified members of the transforming growth factor‐β receptor family as having a role, either directly or indirectly, in signaling from the cell surface by IGFBP‐3. A number of growth factors and hormones stimulate the expression and secretion of cellular IGFBP‐3, which then signals from the cell surface to bring about some of the effects attributed to the primary agents. Within the cell, the apoptosis‐inducing tumor suppressor, p53, can also induce IGFBP‐3 expression and secretion. Since IGFBP‐3 upregulates the cell cycle inhibitor, p21 Waf1 , and increases the ratio of proapoptotic to antiapoptotic members of the Bcl family, it appears to exert the same effects on major downstream targets of cell signaling as p53 does. The nuclear localization of IGFBP‐3 has been described in a number of cell types. IGFBP‐3 may act to import IGFs or other nuclear localization signal‐deficient signaling molecules into the nucleus. It may also act directly in the nucleus by enhancing the activity of retinoid X receptor‐α and thereby promote apoptosis. All of the above phenomena will be discussed with particular emphasis on the growth of breast cancer cells. Microsc. Res. Tech. 59:12–22, 2002. © 2002 Wiley‐Liss, Inc.