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Article

Two novel STK11 missense mutations induce phosphorylation of S6K and promote cell proliferation in Peutz‑Jeghers syndrome

  • Authors:
    • Ran Li
    • Zhiqing Wang
    • Shu Liu
    • Baoping Wu
    • Di Zeng
    • Yali Zhang
    • Lanbo Gong
    • Feihong Deng
    • Haoxuan Zheng
    • Yadong Wang
    • Chudi Chen
    • Junsheng Chen
    • Bo Jiang
  • View Affiliations / Copyright

    Affiliations: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Medical Genetics Center, Guangdong Women and Children's Hospital, Guangzhou, Guangdong 510010, P.R. China, Department of Gastroenterology, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong 511400, P.R. China
  • Pages: 717-726
    |
    Published online on: November 17, 2017
       https://doi.org/10.3892/ol.2017.7436
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Abstract

Peutz‑Jeghers syndrome (PJS) is a rare hereditary disease caused by mutations in serine threonine kinase 11 (STK11) and characterized by an increased risk of developing cancer. Inactivation of STK11 has been associated with the mammalian target of rapamycin (mTOR) pathway. Hyperactivation and phosphorylation of the key downstream target genes ribosomal protein S6 kinase 1 (S6K1) and S6 promote protein synthesis and cell proliferation. To better understand the effects of STK11 dysfunction in the pathogenesis of PJS, genomic DNA samples from 21 patients with PJS from 11 unrelated families were investigated for STK11 mutations in the present study. The results revealed 6 point mutations and 2 large deletions in 8 (72.7%, 8/11) of the unrelated families. Notably, 3 novel mutations were identified, which included 2 missense mutations [c.88G>A (p.Asp30Asn) and c.869T>C (p.Leu290Pro)]. Subsequent immunohistochemical analysis revealed staining for phosphorylated‑S6 protein in colonic hamartoma and breast benign tumor tissues from patients with PJS carrying the two respective missense mutations. Additionally, the novel missense STK11 mutants induced phosphorylation of S6K1 and S6, determined using western blot analysis, and promoted the proliferation of HeLa and SW1116 cells, determined using Cell Counting Kit‑8 and colony formation assays. Collectively, these findings extend the STK11 mutation spectrum and confirm the pathogenicity of two novel missense mutations. This study represents a valuable insight into the molecular mechanisms implicated in the pathogenesis of PJS.
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Copy and paste a formatted citation
Spandidos Publications style
Li R, Wang Z, Liu S, Wu B, Zeng D, Zhang Y, Gong L, Deng F, Zheng H, Wang Y, Wang Y, et al: Two novel STK11 missense mutations induce phosphorylation of S6K and promote cell proliferation in Peutz‑Jeghers syndrome. Oncol Lett 15: 717-726, 2018.
APA
Li, R., Wang, Z., Liu, S., Wu, B., Zeng, D., Zhang, Y. ... Jiang, B. (2018). Two novel STK11 missense mutations induce phosphorylation of S6K and promote cell proliferation in Peutz‑Jeghers syndrome. Oncology Letters, 15, 717-726. https://doi.org/10.3892/ol.2017.7436
MLA
Li, R., Wang, Z., Liu, S., Wu, B., Zeng, D., Zhang, Y., Gong, L., Deng, F., Zheng, H., Wang, Y., Chen, C., Chen, J., Jiang, B."Two novel STK11 missense mutations induce phosphorylation of S6K and promote cell proliferation in Peutz‑Jeghers syndrome". Oncology Letters 15.1 (2018): 717-726.
Chicago
Li, R., Wang, Z., Liu, S., Wu, B., Zeng, D., Zhang, Y., Gong, L., Deng, F., Zheng, H., Wang, Y., Chen, C., Chen, J., Jiang, B."Two novel STK11 missense mutations induce phosphorylation of S6K and promote cell proliferation in Peutz‑Jeghers syndrome". Oncology Letters 15, no. 1 (2018): 717-726. https://doi.org/10.3892/ol.2017.7436
Copy and paste a formatted citation
x
Spandidos Publications style
Li R, Wang Z, Liu S, Wu B, Zeng D, Zhang Y, Gong L, Deng F, Zheng H, Wang Y, Wang Y, et al: Two novel STK11 missense mutations induce phosphorylation of S6K and promote cell proliferation in Peutz‑Jeghers syndrome. Oncol Lett 15: 717-726, 2018.
APA
Li, R., Wang, Z., Liu, S., Wu, B., Zeng, D., Zhang, Y. ... Jiang, B. (2018). Two novel STK11 missense mutations induce phosphorylation of S6K and promote cell proliferation in Peutz‑Jeghers syndrome. Oncology Letters, 15, 717-726. https://doi.org/10.3892/ol.2017.7436
MLA
Li, R., Wang, Z., Liu, S., Wu, B., Zeng, D., Zhang, Y., Gong, L., Deng, F., Zheng, H., Wang, Y., Chen, C., Chen, J., Jiang, B."Two novel STK11 missense mutations induce phosphorylation of S6K and promote cell proliferation in Peutz‑Jeghers syndrome". Oncology Letters 15.1 (2018): 717-726.
Chicago
Li, R., Wang, Z., Liu, S., Wu, B., Zeng, D., Zhang, Y., Gong, L., Deng, F., Zheng, H., Wang, Y., Chen, C., Chen, J., Jiang, B."Two novel STK11 missense mutations induce phosphorylation of S6K and promote cell proliferation in Peutz‑Jeghers syndrome". Oncology Letters 15, no. 1 (2018): 717-726. https://doi.org/10.3892/ol.2017.7436
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