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Mucin 1 enhances the tumor angiogenic response by activation of the AKT signaling pathway

Oncogene volume 31, pages 2187–2198 (2012)Cite this article

Abstract

Although the hyper-glycosylated transmembrane protein Mucin 1 (MUC1) is aberrantly overexpressed in human breast carcinoma, the biological significance of MUC1 overexpression is unclear. This study showed that MUC1 expression promoted the synthesis and secretion of vascular endothelial growth factor (VEGF) through the AKT signaling pathway. Increase VEGF production through MUC1 expression had a number of effect. First, MUC1 transfection increased expression of VEGF in breast cancer cells. Second, MUC1-mediated VEGF induction was attenuated by a chemical inhibitor of AKT or MUC1 knock-down by MUC1 siRNA. Third, MUC1 expression led to the activation of insulin-like growth factor-1 receptor, which correlated with VEGF expression. In addition, when MDA-MB-231 human breast cancer cells were directly injected into NOD/SCID mice, MUC1 expression accelerated xenograft tumor growth in vivo. Finally, MUC1 expression enhanced tumor growth and angiogenesis in a PyMT-MMTV/hMUC1 transgenic mouse model. Concurrent with these results, analysis of a human tissue microarray identified a high correlation between MUC1 and VEGF expression in human breast carcinoma. The current report is the first to demonstrate that MUC1 expression promotes angiogenesis in human breast cancer in vivo and in vitro.

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Acknowledgements

We are grateful to Drs Dong-Young Noh and Hyeong-Gon Moon for providing the human breast cancer tissues microarray. This work was supported in part by grants from the R&D Project, the Ministry of Knowledge Economy (MOST, 10035353) and the Korean Science and Engineering Foundation (KOSEF) through the Tumor Immunity Medical Research Center at Seoul National University college of Medicine, Republic of Korea

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Authors and Affiliations

  1. Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea

    J K Woo & C-W Kim

  2. Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea

    J K Woo, Y Choi, D-H Choi & C-W Kim

  3. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

    J K Woo, Y Choi, D-H Choi & C-W Kim

  4. College of Pharmacy, Gachon University of Medicine and Science, Incheon, Republic of Korea

    S-H Oh

  5. Research Center for Radiotherapy, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea

    J-H Jeong

  6. Department of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea

    H-S Seo

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Woo, J., Choi, Y., Oh, SH. et al. Mucin 1 enhances the tumor angiogenic response by activation of the AKT signaling pathway. Oncogene 31, 2187–2198 (2012). https://doi.org/10.1038/onc.2011.410

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