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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 2014 (10)

Title and authors Publication Year
FoxM1 sustains the Smad3/4 complex and controls transforming growth factor-β signaling and cancer metastasis
Jianfei Xue, Xia Lin, Wen-Tai Chiu, Yao-Hui Chen, Guanzhen Yu, Mingguang Liu, Xin-Hua Feng, Raymond Sawaya, Rene Medema, Mien-Chie Hung, Suyun Huang
Journal of Clinical Investigation 2014
Masking Epistasis Between MYC and TGF-β Pathways in Antiangiogenesis-Mediated Colon Cancer Suppression
M Dews, GS Tan, S Hultine, P Raman, J Choi, EK Duperret, J Lawler, A Bass, A Thomas-Tikhonenko
JNCI Journal of the National Cancer Institute 2014
Metabolic reprogramming during TGFβ1-induced epithelial-to-mesenchymal transition
L Jiang, L Xiao, H Sugiura, X Huang, A Ali, M Kuro-o, RJ Deberardinis, DA Boothman
Oncogene 2014
Tumor suppression in skin and other tissues via cross-talk between vitamin D- and p53-signaling
JÃ Reichrath, S Reichrath, K Heyne, T Vogt, K Roemer
Frontiers in physiology 2014
TP53 supports basal-like differentiation of mammary epithelial cells by preventing translocation of deltaNp63 into nucleoli
PM Munne, Y Gu, M Tumiati, P Gao, S Koopal, S Uusivirta, J Sawicki, GH Wei, SG Kuznetsov
Scientific Reports 2014
Differential expression of centrosome regulators in Her2+ breast cancer cells versus non-tumorigenic MCF10A cells
MY Lee, M Marina, JL King, HI Saavedra
Cell division 2014
Axl as a downstream effector of TGF-β1 via PI3K/Akt-PAK1 signaling pathway promotes tumor invasion and chemoresistance in breast carcinoma
Y Li, L Jia, C Liu, Y Gong, D Ren, N Wang, X Zhang, Y Zhao
Tumor Biology 2014
TSPAN12 is a critical factor for cancer–fibroblast cell contact-mediated cancer invasion
R Otomo, C Otsubo, Y Matsushima-Hibiya, M Miyazaki, F Tashiro, H Ichikawa, T Kohno, T Ochiya, J Yokota, H Nakagama, Y Taya, M Enari
Proceedings of the National Academy of Sciences 2014
The MDM2 gene family
M Mendoza, G Mandani, J Momand
BioMolecular Concepts 2014
Targeting MDM2-p53 interaction for cancer therapy: are we there yet?
Nag S, Zhang X, Srivenugopal KS, Wang MH, Wang W, Zhang R
Current medicinal chemistry 2014

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