Γ-secretase components as predictors of breast cancer outcome.

γ-secretase is a large ubiquitously expressed protease complex composed of four core subunits: presenilin, Aph1, PEN-2, and nicastrin. The function of γ-secretase in the cells is to proteolytically cleave various proteins within their transmembrane domains. Presenilin and Aph1 occur as alternative v...

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Autores principales:	Hanna M Peltonen, Annakaisa Haapasalo, Mikko Hiltunen, Vesa Kataja, Veli-Matti Kosma, Arto Mannermaa
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/83fb7fe22f0c41e89e9376c0fc15e297
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spelling	oai:doaj.org-article:83fb7fe22f0c41e89e9376c0fc15e2972021-11-18T08:48:41ZΓ-secretase components as predictors of breast cancer outcome.1932-620310.1371/journal.pone.0079249https://doaj.org/article/83fb7fe22f0c41e89e9376c0fc15e2972013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24223915/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203γ-secretase is a large ubiquitously expressed protease complex composed of four core subunits: presenilin, Aph1, PEN-2, and nicastrin. The function of γ-secretase in the cells is to proteolytically cleave various proteins within their transmembrane domains. Presenilin and Aph1 occur as alternative variants belonging to mutually exclusive γ-secretase complexes and providing the complexes with heterogeneous biochemical and physiological properties. γ-secretase is proposed to have a role in the development and progression of cancer and γ-secretase inhibitors are intensively studied for their probable anti-tumor effects in various types of cancer models. Here, we for the first time determined mRNA expression levels of presenilin-1, presenilin-2, Aph1a, Aph1b, PEN-2, and nicastrin in a set of breast cancer tissue samples (N = 55) by quantitative real-time PCR in order to clarify the clinical significance of the expression of different γ-secretase complex components in breast cancer. We found a high positive correlation between the subunit expression levels implying a common regulation of transcription. Our univariate Kaplan-Meier survival analyses established low expression level of γ-secretase complex as a risk factor for breast cancer specific mortality. The tumors expressing low levels of γ-secretase complex were characterized by high histopathological tumor grade, low or no expression of estrogen and progesterone receptors and consequently high probability to fall into the class of triple negative breast cancer tumors. These results may provide novel tools to further categorize breast cancer tumors, especially the highly aggressive and poorly treatable breast cancer type of triple negative cases, and suggest a significant role for γ-secretase in breast cancer.Hanna M PeltonenAnnakaisa HaapasaloMikko HiltunenVesa KatajaVeli-Matti KosmaArto MannermaaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e79249 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hanna M Peltonen Annakaisa Haapasalo Mikko Hiltunen Vesa Kataja Veli-Matti Kosma Arto Mannermaa Γ-secretase components as predictors of breast cancer outcome.
description	γ-secretase is a large ubiquitously expressed protease complex composed of four core subunits: presenilin, Aph1, PEN-2, and nicastrin. The function of γ-secretase in the cells is to proteolytically cleave various proteins within their transmembrane domains. Presenilin and Aph1 occur as alternative variants belonging to mutually exclusive γ-secretase complexes and providing the complexes with heterogeneous biochemical and physiological properties. γ-secretase is proposed to have a role in the development and progression of cancer and γ-secretase inhibitors are intensively studied for their probable anti-tumor effects in various types of cancer models. Here, we for the first time determined mRNA expression levels of presenilin-1, presenilin-2, Aph1a, Aph1b, PEN-2, and nicastrin in a set of breast cancer tissue samples (N = 55) by quantitative real-time PCR in order to clarify the clinical significance of the expression of different γ-secretase complex components in breast cancer. We found a high positive correlation between the subunit expression levels implying a common regulation of transcription. Our univariate Kaplan-Meier survival analyses established low expression level of γ-secretase complex as a risk factor for breast cancer specific mortality. The tumors expressing low levels of γ-secretase complex were characterized by high histopathological tumor grade, low or no expression of estrogen and progesterone receptors and consequently high probability to fall into the class of triple negative breast cancer tumors. These results may provide novel tools to further categorize breast cancer tumors, especially the highly aggressive and poorly treatable breast cancer type of triple negative cases, and suggest a significant role for γ-secretase in breast cancer.
format	article
author	Hanna M Peltonen Annakaisa Haapasalo Mikko Hiltunen Vesa Kataja Veli-Matti Kosma Arto Mannermaa
author_facet	Hanna M Peltonen Annakaisa Haapasalo Mikko Hiltunen Vesa Kataja Veli-Matti Kosma Arto Mannermaa
author_sort	Hanna M Peltonen
title	Γ-secretase components as predictors of breast cancer outcome.
title_short	Γ-secretase components as predictors of breast cancer outcome.
title_full	Γ-secretase components as predictors of breast cancer outcome.
title_fullStr	Γ-secretase components as predictors of breast cancer outcome.
title_full_unstemmed	Γ-secretase components as predictors of breast cancer outcome.
title_sort	γ-secretase components as predictors of breast cancer outcome.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/83fb7fe22f0c41e89e9376c0fc15e297
work_keys_str_mv	AT hannampeltonen gsecretasecomponentsaspredictorsofbreastcanceroutcome AT annakaisahaapasalo gsecretasecomponentsaspredictorsofbreastcanceroutcome AT mikkohiltunen gsecretasecomponentsaspredictorsofbreastcanceroutcome AT vesakataja gsecretasecomponentsaspredictorsofbreastcanceroutcome AT velimattikosma gsecretasecomponentsaspredictorsofbreastcanceroutcome AT artomannermaa gsecretasecomponentsaspredictorsofbreastcanceroutcome
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Γ-secretase components as predictors of breast cancer outcome.

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