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Clinicopathological significance of p38β, p38γ, and p38δ and its biological roles in esophageal squamous cell carcinoma

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Tumor Biology

Abstract

P38β, p38γ, and p38δ have been sporadically and scarcely reported to be involved in the carcinogenesis of cancers, compared with p38α isoform. However, little has been known regarding their clinicopathological significance and biological roles in esophageal squamous cell carcinoma (ESCC). Expression status of p38β, p38γ, and p38δ was assayed using immunohistochemistry with ESCC tissue microarray; ensuing clinicopathological significance was statistically analyzed. To define its biological roles on proliferation, migration and invasion of ESCC cell line Eca109 in vitro, MTT, wound healing, and Transwell assays were employed, respectively. As confirmation, athymic nude mice were taken to verify the effect over proliferation in vivo. It was found that both p38β and p38δ expression, other than p38γ, were significantly higher in ESCC tissues compared with paired normal controls. In terms of prognosis, only p38β expression was observed to be significantly associated with overall prognosis. Clinicopathologically, there was significant association between p38γ expression and clinical stage, lymph nodes metastases, and tumor volume. No significant association was found for p38β and p38δ between its expression and other clinicopathological parameters other than significant difference of expression between ESCC versus normal control. In Eca109, it was observed that p38β, p38γ, and p38δ can promote the cell growth and motility. As verification, over-expression of p38δ can promote, whereas knockdown of p38γ can prevent, the tumorigenesis in nude mice model xenografted with Eca109 cells whose basal level of p38δ was stably over-expressed and p38γ was stably knocked down. Together, our results demonstrate that p38β, p38γ, and p38δ played oncogenic roles in ESCC.

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Acknowledgments

The study was supported by National Science Foundation of China (no. 81360357, 81160303, 81260359, 81201891, U1303321), from Major Science and Technology Projects of the Xinjiang Uygur Autonomous Region (no. 201430123-1) and Opening Project of Xinjiang Medical Animal Model Research Key Laboratory (XJDX1103-2012-05). We are especially appreciative of Professor Ana Cuenda in the Department of Immunology and Oncology, Centro National de Biotecnología/CSIC, Madrid, Spain, for kindly proof reading and giving constructive comments in the manuscript.

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Authors and Affiliations

  1. Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, China

    Shutao Zheng, Chenchen Yang, Tao Liu, Qing Liu, Fang Dai & Xiaomei Lu

  2. State Key Lab Incubation Base of Xinjiang Major Diseases Research, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, China

    Shutao Zheng, Chenchen Yang, Tao Liu, Qing Liu, Fang Dai, Ilyar Sheyhidin & Xiaomei Lu

  3. Clinical Medical Research Institute, State Key Lab Breeding Base of Xinjiang Major Diseases Research, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang Uygur Autonomous Region, China

    Xiaomei Lu

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  1. Shutao Zheng
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Zheng, S., Yang, C., Liu, T. et al. Clinicopathological significance of p38β, p38γ, and p38δ and its biological roles in esophageal squamous cell carcinoma. Tumor Biol. 37, 7255–7266 (2016). https://doi.org/10.1007/s13277-015-4610-9

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  • DOI: https://doi.org/10.1007/s13277-015-4610-9

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