Transcriptional and posttranslational regulation of insulin-like growth factor binding protein-3 by Akt3

Quanri Jin, Hyo Jong Lee, Hye Young Min, John K endal Smith, Su J ung Hwang, Young M i Whang, Woo Young Kim, Yeul Hong Kim, Ho Young Lee

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)2232-2243
Number of pages12
JournalCarcinogenesis
Volume35
Issue number10
DOIs
Publication statusPublished - 2014 Oct 1

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Insulin-Like Growth Factor Binding Protein 3
Non-Small Cell Lung Carcinoma
Protein Stability
RNA Stability
Somatomedins
Heterografts

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Jin, Q., Lee, H. J., Min, H. Y., Smith, J. K. E., Hwang, S. J. U., Whang, Y. M. I., ... Lee, H. Y. (2014). Transcriptional and posttranslational regulation of insulin-like growth factor binding protein-3 by Akt3. Carcinogenesis, 35(10), 2232-2243. https://doi.org/10.1093/carcin/bgu129

Transcriptional and posttranslational regulation of insulin-like growth factor binding protein-3 by Akt3. / Jin, Quanri; Lee, Hyo Jong; Min, Hye Young; Smith, John K endal; Hwang, Su J ung; Whang, Young M i; Kim, Woo Young; Kim, Yeul Hong; Lee, Ho Young.

In: Carcinogenesis, Vol. 35, No. 10, 01.10.2014, p. 2232-2243.

Research output: Contribution to journalArticle

Jin, Q, Lee, HJ, Min, HY, Smith, JKE, Hwang, SJU, Whang, YMI, Kim, WY, Kim, YH & Lee, HY 2014, 'Transcriptional and posttranslational regulation of insulin-like growth factor binding protein-3 by Akt3', Carcinogenesis, vol. 35, no. 10, pp. 2232-2243. https://doi.org/10.1093/carcin/bgu129
Jin, Quanri ; Lee, Hyo Jong ; Min, Hye Young ; Smith, John K endal ; Hwang, Su J ung ; Whang, Young M i ; Kim, Woo Young ; Kim, Yeul Hong ; Lee, Ho Young. / Transcriptional and posttranslational regulation of insulin-like growth factor binding protein-3 by Akt3. In: Carcinogenesis. 2014 ; Vol. 35, No. 10. pp. 2232-2243.
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