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LASS2/TMSG1 inhibits growth and invasion of breast cancer cell in vitro through regulation of vacuolar ATPase activity

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Tumor Biology

Abstract

Homo sapiens longevity assurance homologue 2 of yeast LAG1 (LASS2)/tumor metastasis suppressor gene 1 (TMSG1) was a novel tumor metastasis-related gene identified using messenger RNA differential display from non-metastatic human prostate cancer cell variants. The mechanism of LASS2/TMSG1 inhibiting tumor invasion metastasis in breast cancer cells had not been well investigated. In the present study, a full length of 1.2 kb LASS2/TMSG1 complementary DNA (cDNA) coding for a protein of 380 amino acids was cloned. PcDNA3 eukaryotic expression plasmids of LASS2/TMSG1 were constructed and transfected into human breast cancer cell line MCF-7 by lipofectin transfection method. And, the biological effects were observed comparing with control groups. As the result, LASS2/TMSG1 inhibited cell growth in vitro by increasing apoptosis and changing cell cycle distribution. Furthermore, the vacuolar ATPase (V-ATPase) activity and extracellular hydrogen ion concentration were significantly decreased and the activity of secreted matrix metalloproteinase-2 (MMP-2) was downregulated in MCF-7 cells overexpressing LASS2/TMSG1 compared with the controls. Therefore, LASS2/TMSG1 may inhibit growth and invasion of breast cancer cell in vitro through decreasing V-ATPase activity and extracellular hydrogen ion concentration and inactivating secreted MMP-2. The findings provided the evidence that the LASS2/TMSG1 gene had tumor growth and invasion suppressor function in human breast cancer cell and may provide a promising target for cancer metastasis diagnosis and therapy.

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Acknowledgments

The article was supported by the National Sciences Foundation of China (30971142). Thanks to Beiying Liu for data analysis and figure modification.

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Authors and Affiliations

  1. Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Haidian District, 100191, Beijing, China

    Fang Mei, Jiangfeng You, Mengxue Zhang, Jiangying Liu, Bo Zhang & Fei Pei

  2. School of Mechanical Engineering, University of Science & Technology Beijing, Beijing, China

    Beiying Liu

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  1. Fang Mei
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  2. Jiangfeng You
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  3. Beiying Liu
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  4. Mengxue Zhang
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Correspondence to Fei Pei.

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Mei, F., You, J., Liu, B. et al. LASS2/TMSG1 inhibits growth and invasion of breast cancer cell in vitro through regulation of vacuolar ATPase activity. Tumor Biol. 36, 2831–2844 (2015). https://doi.org/10.1007/s13277-014-2910-0

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  • DOI: https://doi.org/10.1007/s13277-014-2910-0

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