Abstract
BackgroundInsulin-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.Methodology/Principal FindingsWe 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.Conclusion/SignificanceThese 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.
Highlights
Insulin-like growth factor binding proteins (IGFBPs) belong to a family of cysteine-rich multifunctional proteins that bind IGF with high affinities
Northern blot analysis revealed that the rhIGFBP-3 transcripts could be detected in transformants carrying the constructs, pSB130/Gt1/hIGFBP-3 (B), pSB130/Gt1/SP/hIGFBP-3 (SB), and pSB130/Gt1/SP/ hIGFBP-3/KDEL (SBK) (Figure S1)
Signals were found in transformants harboring the constructs with glutelin signal peptide, pSB130/Gt1/SP/hIGFBP-3 (SB) and pSB130/Gt1/SP/hIGFBP-3/KDEL (SBK) only, whereas no bands were detected in transformant carrying the promoter only construct, pSB130/Gt1/hIGFBP-3 (B) and wild type plant
Summary
Insulin-like growth factor binding proteins (IGFBPs) belong to a family of cysteine-rich multifunctional proteins that bind IGF with high affinities. 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. 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. Conclusion/Significance: 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
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