Original Article | Published:

Upregulation of mitogen-inducible gene 6 triggers antitumor effect and attenuates progesterone resistance in endometrial carcinoma cells

Cancer Gene Therapy volume 22, pages 536541 (2015) | Download Citation

Abstract

Researches regarding mitogen-inducible gene 6 (Mig-6) have confirmed its role as a tumor suppressor and progesterone resistance factor in endometrium. In this study, after confirming the downregulation of Mig-6 protein in endometrial carcinoma (EC) tissues, the expression of Mig-6 was upregulated in Ishikawa cells by pCMV6-Mig-6 plasmid. We observed the increased apoptosis, decreased proliferation and invasion potential of Ishikawa cells after upregulation of Mig-6. The proapoptosis ability of P4 significantly enhanced by 39.36%, the antiproliferation ability increased by 37.90% and the anti-invasion ability increased by 48.89%, suggesting the antiprogesterone resistance potential of Mig-6 in endometrium. In addition, the results suggested that Mig-6 may induce Ishikawa cell apoptosis through the mitochondrial pathway, inhibit cell proliferation via the extracellular signal-regulated kinase pathway and the anti-invasion potential may associate with matrix metalloproteinase (MMP)-2 and MMP-9 downexpression. Therefore, upregulation of Mig-6 may add a new strategy to suppress endometrial tumorigenesis and attenuate the progesterone resistance during P4 treatment.

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Acknowledgements

This work was supported by Grant 81070471 from the National Natural Science Foundation of China and Grant RC201161 from Developing Health Engineering Fund Project of Jiangsu Province of China. We thank the State Key Laboratory of Reproduction Medicine at The First Affiliated Hospital of Nanjing Medical University for excellent technical assistance. This study was done in the Laboratory of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University (also named Jiangsu Province Hospital).

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  1. Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University (also named Jiangsu Province Hospital), Nanjing, People’s Republic of China

    • W Xu
    • , S Zhu
    • , Y Zhou
    • , Y Jin
    • , H Dai
    •  & X Wang

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The authors declare no conflict of interest.

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Correspondence to X Wang.

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DOI

https://doi.org/10.1038/cgt.2015.52

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