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

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 exp...

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Autores principales:	Shinsuke Oda, Masayoshi Fujisawa, Li Chunning, Toshihiro Ito, Takahiro Yamaguchi, Teizo Yoshimura, Akihiro Matsukawa
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9103982ed00348f99c05e05f25c70648
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spelling	oai:doaj.org-article:9103982ed00348f99c05e05f25c706482021-12-02T20:16:11ZExpression of Spred2 in the urothelial tumorigenesis of the urinary bladder.1932-620310.1371/journal.pone.0254289https://doaj.org/article/9103982ed00348f99c05e05f25c706482021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254289https://doaj.org/toc/1932-6203Aberrant 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.Shinsuke OdaMasayoshi FujisawaLi ChunningToshihiro ItoTakahiro YamaguchiTeizo YoshimuraAkihiro MatsukawaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11, p e0254289 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shinsuke Oda Masayoshi Fujisawa Li Chunning Toshihiro Ito Takahiro Yamaguchi Teizo Yoshimura Akihiro Matsukawa Expression of Spred2 in the urothelial tumorigenesis of the urinary bladder.
description	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.
format	article
author	Shinsuke Oda Masayoshi Fujisawa Li Chunning Toshihiro Ito Takahiro Yamaguchi Teizo Yoshimura Akihiro Matsukawa
author_facet	Shinsuke Oda Masayoshi Fujisawa Li Chunning Toshihiro Ito Takahiro Yamaguchi Teizo Yoshimura Akihiro Matsukawa
author_sort	Shinsuke Oda
title	Expression of Spred2 in the urothelial tumorigenesis of the urinary bladder.
title_short	Expression of Spred2 in the urothelial tumorigenesis of the urinary bladder.
title_full	Expression of Spred2 in the urothelial tumorigenesis of the urinary bladder.
title_fullStr	Expression of Spred2 in the urothelial tumorigenesis of the urinary bladder.
title_full_unstemmed	Expression of Spred2 in the urothelial tumorigenesis of the urinary bladder.
title_sort	expression of spred2 in the urothelial tumorigenesis of the urinary bladder.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/9103982ed00348f99c05e05f25c70648
work_keys_str_mv	AT shinsukeoda expressionofspred2intheurothelialtumorigenesisoftheurinarybladder AT masayoshifujisawa expressionofspred2intheurothelialtumorigenesisoftheurinarybladder AT lichunning expressionofspred2intheurothelialtumorigenesisoftheurinarybladder AT toshihiroito expressionofspred2intheurothelialtumorigenesisoftheurinarybladder AT takahiroyamaguchi expressionofspred2intheurothelialtumorigenesisoftheurinarybladder AT teizoyoshimura expressionofspred2intheurothelialtumorigenesisoftheurinarybladder AT akihiromatsukawa expressionofspred2intheurothelialtumorigenesisoftheurinarybladder
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Expression of Spred2 in the urothelial tumorigenesis of the urinary bladder.

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