title: Inhibition of human MCF-7 breast cancer cells and HT-29 colon cancer cells by rice-produced recombinant human insulin-like growth binding protein-3 (rhIGFBP-3).
abstract: BACKGROUND
  Insulin-like growth factor binding protein-3 (IGFBP-3) is a multifunctional molecule which is closely related to cell growth, apoptosis, angiogenesis, metabolism and senescence. It combines with insulin-like growth factor-I (IGF-I) to form a complex (IGF-I/IGFBP-3) that can treat growth hormone insensitivity syndrome (GHIS) and reduce insulin requirement in patients with diabetes. IGFBP-3 alone has been shown to have anti-proliferation effect on numerous cancer cells.
  
  
  RESULTS
  We reported here an expression method to produce functional recombinant human IGFBP-3 (rhIGFBP-3) in transgenic rice grains. Protein sorting sequences, signal peptide and endoplasmic reticulum retention tetrapeptide (KDEL) were included in constructs for enhancing rhIGFBP-3 expression. Western blot analysis showed that only the constructs with signal peptide were successfully expressed in transgenic rice grains. Both rhIGFBP-3 proteins, with or without KDEL sorting sequence inhibited the growth of MCF-7 human breast cancer cells (65.76 ± 1.72% vs 45.00 ± 0.86%, p < 0.05; 50.84 ± 1.97% vs 45.00 ± 0.86%, p < 0.01 respectively) and HT-29 colon cancer cells (65.14 ± 3.84% vs 18.01 ± 13.81%, p < 0.05 and 54.7 ± 9.44% vs 18.01 ± 13.81%, p < 0.05 respectively) when compared with wild type rice.
  
  
  CONCLUSIONS
  These findings demonstrated the feasibility of producing biological active rhIGFBP-3 in rice using a transgenic approach, which will definitely encourage more research on the therapeutic use of hIGFBP-3 in future.
authors.affiliation: State Key Laboratory of Agrobiotechnology, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China ; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China.
authors.forename: Stanley C K
authors.initials: SC
authors.lastname: Cheung
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Long
authors.forename: Lizhong
authors.initials: L
authors.lastname: Liu
authors.forename: Qiaoquan
authors.initials: Q
authors.lastname: Liu
authors.forename: Linlin
authors.initials: L
authors.lastname: Lan
authors.forename: Peter C Y
authors.initials: PC
authors.lastname: Tong
authors.forename: Samuel S M
authors.initials: SS
authors.lastname: Sun
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D006031:Glycosylation; D019073:HT29 Cells; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D061986:MCF-7 Cells; D012275:Oryza / Q000235:genetics*; D030821:Plants, Genetically Modified; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins