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Citations to this article

TGF-β1–induced expression of human Mdm2 correlates with late-stage metastatic breast cancer
Shinako Araki, … , David A. Boothman, Lindsey D. Mayo
Shinako Araki, … , David A. Boothman, Lindsey D. Mayo
Published December 1, 2009
Citation Information: J Clin Invest. 2010;120(1):290-302. https://doi.org/10.1172/JCI39194.
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Research Article Oncology Article has an altmetric score of 10

TGF-β1–induced expression of human Mdm2 correlates with late-stage metastatic breast cancer

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Abstract

The E3 ubiquitin ligase human murine double minute (HDM2) is overexpressed in 40%–80% of late-stage metastatic cancers in the absence of gene amplification. Hdm2 regulates p53 stability via ubiquitination and has also been implicated in altering the sensitivity of cells to TGF-β1. Whether TGF-β1 signaling induces Hdm2 expression leading to HDM2-mediated destabilization of p53 has not been investigated. In this study, we report that TGF-β1–activated SMA- and MAD3 (Smad3/4) transcription factors specifically bound to the second promoter region of HDM2, leading to increased HDM2 protein expression and destabilization of p53 in human cancer cell lines. Additionally, TGF-β1 expression led to Smad3 activation and murine double minute 2 (Mdm2) expression in murine mammary epithelial cells during epithelial-to-mesenchymal transition (EMT). Furthermore, histological analyses of human breast cancer samples demonstrated that approximately 65% of late-stage carcinomas were positive for activated Smad3 and HDM2, indicating a strong correlation between TGF-β1–mediated induction of HDM2 and late-stage tumor progression. Identification of Hdm2 as a downstream target of TGF-β1 represents a critical prosurvival mechanism in cancer progression and provides another point for therapeutic intervention in late-stage cancer.

Authors

Shinako Araki, Jacob A. Eitel, Christopher N. Batuello, Khadijeh Bijangi-Vishehsaraei, Xian-Jin Xie, David Danielpour, Karen E. Pollok, David A. Boothman, Lindsey D. Mayo

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 Total
Citations: 2 4 5 1 5 2 8 3 5 2 3 10 5 15 7 6 83
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2016 (2)

Title and authors Publication Year
Estrogen receptor alpha (ERα/ESR1) mediates the p53-independent overexpression of MDM4/MDMX and MDM2 in human breast cancer
WM Swetzig, J Wang, GM Das
Oncotarget 2016
Dichotomous roles of TGF-β in human cancer
JJ Huang, GC Blobe
Biochemical Society Transactions 2016

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