Transcriptional and posttranslational regulation of insulin-like growth factor binding protein-3 by Akt3
- Authors
- Jin, Quanri; Lee, Hyo-Jong; Min, Hye-Young; Smith, John Kendal; Hwang, Su Jung; Whang, Young Mi; Kim, Woo-Young; Kim, Yeul Hong; Lee, Ho-Young
- Issue Date
- 10월-2014
- Publisher
- OXFORD UNIV PRESS
- Citation
- CARCINOGENESIS, v.35, no.10, pp.2232 - 2243
- Indexed
- SCIE
SCOPUS
- Journal Title
- CARCINOGENESIS
- Volume
- 35
- Number
- 10
- Start Page
- 2232
- End Page
- 2243
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/97236
- DOI
- 10.1093/carcin/bgu129
- ISSN
- 0143-3334
- Abstract
- Insulin-like growth factor (IGF)-dependent and -independent antitumor activities of insulin-like growth factor binding protein-3 (IGFBP-3) have been proposed in human non-small cell lung cancer (NSCLC) cells. However, the mechanism underlying regulation of IGFBP-3 expression in NSCLC cells is not well understood. In this study, we show that activation of Akt, especially Akt3, plays a major role in the mRNA expression and protein stability of IGFBP-3 and thus antitumor activities of IGFBP-3 in NSCLC cells. When Akt was activated by genomic or pharmacologic approaches, IGFBP-3 transcription and protein stability were decreased. Conversely, suppression of Akt increased IGFBP-3 mRNA levels and protein stability in NSCLC cell lines. Characterization of the effects of constitutively active form of each Akt subtype (HA-Akt-DD) on IGFBP-3 expression in NSCLC cells and a xenograft model indicated that Akt3 plays a major role in the Akt-mediated regulation of IGFBP-3 expression and thus suppression of Akt effectively enhances the antitumor activities of IGFBP-3 in NSCLC cells with Akt3 overactivation. Collectively, these data suggest a novel function of Akt3 as a negative regulator of IGFBP-3, indicating the possible benefit of a combined inhibition of IGFBP-3 and Akt3 for the treatment of patients with NSCLC.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.