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  • Original Paper
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The MCT-1 oncogene product impairs cell cycle checkpoint control and transforms human mammary epithelial cells

Oncogene volume 24, pages 4956–4964 (2005)Cite this article

Abstract

Multiple copies in T-cell maligancy (MCT-1) is a putative oncogene initially identified in a human T-cell lymphoma. Forced expression of MCT-1 has recently been shown to induce cell transformation and proliferation, as well as to activate survival-related PI-3K/AKT pathways protecting cells from apoptosis. MCT-1 protein is stabilized in response to DNA damage. The impact of MCT-1 overexpression on DNA damage response remains unknown. Here, we show that MCT-1 deregulates cell cycle checkpoints. The phosphorylation of genomic stabilizers H2AX and NBS1 are enhanced in MCT-1-overexpressing cells. Forced expression of MCT-1 significantly increases the number of DNA damage-induced foci involving γ-H2AX and 53BP1. In MCT-1-overexpressing cells, the proportion of S-phase cell population is preferentially increased after exposure to γ-irradiation compared to controls. Knockdown of endogenous MCT-1 using an siRNA approach attenuates the H2AX phosphorylation and the G1/S checkpoint defect. Furthermore, MCT-1 is capable of transforming immortalized human mammary epithelial cells and promoting genomic instability. These data shed light on the role of MCT-1 in the cellular response to DNA damage and its involvement in malignant transformation.

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Acknowledgements

We thank Dr V Graig Jordan and Dr Yossi Shiloh for helpful discussions and providing reagents, and Anne Croisetiere and Dr Bin Chen for technical support. A Merit Review Award from the Department of Veterans Affairs (RBG) and Avon Foundation Pilot Project Award (RBG) supported this work.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine and the Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, 60611, IL, USA

    Hsin-Ling Hsu, Bo Shi & Ronald B Gartenhaus

  2. Division of Molecular and Genomic Medicine, National Health Research Institutes, 128 Yen-Chiu-Yuan Road, Sec. 2, Taipei, 115, Taiwan

    Hsin-Ling Hsu

  3. University of Maryland Greenebaum Cancer Center, 9-011 BRB, 655 West Baltimore Street, Baltimore, 21201, MD, USA

    Ronald B Gartenhaus

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  1. Hsin-Ling Hsu
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  2. Bo Shi
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Correspondence to Ronald B Gartenhaus.

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Hsu, HL., Shi, B. & Gartenhaus, R. The MCT-1 oncogene product impairs cell cycle checkpoint control and transforms human mammary epithelial cells. Oncogene 24, 4956–4964 (2005). https://doi.org/10.1038/sj.onc.1208680

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