This gene is a member of the insulin-like growth factor-binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.
IGFBP3 protein levels decrease during the progression of prostate cancer from benign to metastatic disease. Although, production of the protein does not cease completely. IGFBP3 is still made (at a lower level) by prostate cancer cells and secreted into the surrounding environment. However, instead of the full length, functional protein, IGFBP3 is found to be cleaved. This prevents IGFBP3 from binding and sequestering IGFs and the growth factors are free to bind the IGF-1R and promote cell survival.
^Cubbage ML, Suwanichkul A, Powell DR (July 1990). "Insulin-like growth factor binding protein-3. Organization of the human chromosomal gene and demonstration of promoter activity". J. Biol. Chem.265 (21): 12642–9. PMID1695633.
^Miyake H, Pollak M, Gleave ME (June 2000). "Castration-induced up-regulation of insulin-like growth factor binding protein-5 potentiates insulin-like growth factor-I activity and accelerates progression to androgen independence in prostate cancer models". Cancer Res.60 (11): 3058–64. PMID10850457. For IGFBP-3 it refers to "Differential expression of insulin-like growth factor binding proteins in high versus low Gleason score prostate cancer.". J. Urol.159 (4): 1379–83. 1998. PMID9507888.
^Birnbaum RS, Ware JL, Plymate SR (June 1994). "Insulin-like growth factor-binding protein-3 expression and secretion by cultures of human prostate epithelial cells and stromal fibroblasts". J. Endocrinol.141 (3): 535–40. doi:10.1677/joe.0.1410535. PMID7520932.
^ abcTwigg, S M; Baxter R C (March 1998). "Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit". J. Biol. Chem. (UNITED STATES) 273 (11): 6074–9. doi:10.1074/jbc.273.11.6074. ISSN0021-9258. PMID9497324.
^ abcFirth, S M; Ganeshprasad U, Baxter R C (January 1998). "Structural determinants of ligand and cell surface binding of insulin-like growth factor-binding protein-3". J. Biol. Chem. (UNITED STATES) 273 (5): 2631–8. doi:10.1074/jbc.273.5.2631. ISSN0021-9258. PMID9446566.
^ abBuckway, C K; Wilson E M, Ahlsén M, Bang P, Oh Y, Rosenfeld R G (October 2001). "Mutation of three critical amino acids of the N-terminal domain of IGF-binding protein-3 essential for high affinity IGF binding". J. Clin. Endocrinol. Metab. (United States) 86 (10): 4943–50. doi:10.1210/jc.86.10.4943. ISSN0021-972X. PMID11600567.
^Cohen, P; Graves H C, Peehl D M, Kamarei M, Giudice L C, Rosenfeld R G (October 1992). "Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma". J. Clin. Endocrinol. Metab. (UNITED STATES) 75 (4): 1046–53. doi:10.1210/jc.75.4.1046. ISSN0021-972X. PMID1383255.
^Storch, S; Kübler B, Höning S, Ackmann M, Zapf J, Blum W, Braulke T (December 2001). "Transferrin binds insulin-like growth factors and affects binding properties of insulin-like growth factor binding protein-3". FEBS Lett. (Netherlands) 509 (3): 395–8. doi:10.1016/S0014-5793(01)03204-5. ISSN0014-5793. PMID11749962.
^Shi, Z; Xu W, Loechel F, Wewer U M, Murphy L J (June 2000). "ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3". J. Biol. Chem. (UNITED STATES) 275 (24): 18574–80. doi:10.1074/jbc.M002172200. ISSN0021-9258. PMID10849447.
^Loechel, F; Fox J W, Murphy G, Albrechtsen R, Wewer U M (November 2000). "ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3". Biochem. Biophys. Res. Commun. (UNITED STATES) 278 (3): 511–5. doi:10.1006/bbrc.2000.3835. ISSN0006-291X. PMID11095942.
^Mochizuki, S; Shimoda M, Shiomi T, Fujii Y, Okada Y (February 2004). "ADAM28 is activated by MMP-7 (matrilysin-1) and cleaves insulin-like growth factor binding protein-3". Biochem Biophys Res Commun (Elsevier) 315 (1): 79–84. doi:10.1016/j.bbrc.2004.01.022. PMID15013428.
^Weinzimer, S A; Gibson T B, Collett-Solberg P F, Khare A, Liu B, Cohen P (April 2001). "Transferrin is an insulin-like growth factor-binding protein-3 binding protein". J. Clin. Endocrinol. Metab. (United States) 86 (4): 1806–13. doi:10.1210/jc.86.4.1806. ISSN0021-972X. PMID11297622.
^Martin, J A; Miller B A, Scherb M B, Lembke L A, Buckwalter J A (July 2002). "Co-localization of insulin-like growth factor binding protein 3 and fibronectin in human articular cartilage". Osteoarthr. Cartil. (England) 10 (7): 556–63. doi:10.1053/joca.2002.0791. ISSN1063-4584. PMID12127836.
^Gui, Y; Murphy L J (May. 2001). "Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) binds to fibronectin (FN): demonstration of IGF-I/IGFBP-3/fn ternary complexes in human plasma". J. Clin. Endocrinol. Metab. (United States) 86 (5): 2104–10. doi:10.1210/jc.86.5.2104. ISSN0021-972X. PMID11344214.
^Campbell, P G; Durham S K, Suwanichkul A, Hayes J D, Powell D R (August 1998). "Plasminogen binds the heparin-binding domain of insulin-like growth factor-binding protein-3". Am. J. Physiol. (UNITED STATES) 275 (2 Pt 1): E321–31. ISSN0002-9513. PMID9688635.
^Liu, B; Lee H Y, Weinzimer S A, Powell D R, Clifford J L, Kurie J M, Cohen P (October 2000). "Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-alpha regulate transcriptional signaling and apoptosis". J. Biol. Chem. (UNITED STATES) 275 (43): 33607–13. doi:10.1074/jbc.M002547200. ISSN0021-9258. PMID10874028.