論文

最終著者 責任著者 国際誌
2021年

Expression of Spred2 in the urothelial tumorigenesis of the urinary bladder.

PloS one
  • Shinsuke Oda
  • ,
  • Masayoshi Fujisawa
  • ,
  • Li Chunning
  • ,
  • Toshihiro Ito
  • ,
  • Takahiro Yamaguchi
  • ,
  • Teizo Yoshimura
  • ,
  • Akihiro Matsukawa

16
11
開始ページ
e0254289
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0254289

Aberrant activation of the Ras/Raf/ERK (extracellular-signal-regulated kinase)-MAPK (mitogen-activated protein kinase) pathway is involved in the progression of cancer, including urothelial carcinoma; but the negative regulation remains unclear. In the present study, we investigated pathological expression of Spred2 (Sprouty-related EVH1 domain-containing protein 2), a negative regulator of the Ras/Raf/ERK-MAPK pathway, and the relation to ERK activation and Ki67 index in various categories of 275 urothelial tumors obtained from clinical patients. In situ hybridization demonstrated that Spred2 mRNA was highly expressed in high-grade non-invasive papillary urothelial carcinoma (HGPUC), and the expression was decreased in carcinoma in situ (CIS) and infiltrating urothelial carcinoma (IUC). Immunohistochemically, membranous Spred2 expression, important to interact with Ras/Raf, was preferentially found in HGPUC. Interestingly, membranous Spred2 expression was decreased in CIS and IUC relative to HGPUC, while ERK activation and the expression of the cell proliferation marker Ki67 index were increased. HGPUC with membranous Spred2 expression correlated significantly with lower levels of ERK activation and Ki67 index as compared to those with negative Spred2 expression. Thus, our pathological findings suggest that Spred2 counters cancer progression in non-invasive papillary carcinoma possibly through inhibiting the Ras/Raf/ERK-MAPK pathway, but this regulatory mechanism is lost in cancers with high malignancy. Spred2 appears to be a key regulator in the progression of non-invasive bladder carcinoma.

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0254289
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34818323
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612556
ID情報
  • DOI : 10.1371/journal.pone.0254289
  • PubMed ID : 34818323
  • PubMed Central 記事ID : PMC8612556

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