AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins

The purpose of this study was to elucidate the mechanisms associated with the specific effects of AKT1 and AKT2 isoforms in breast cancer progression. We modulated the abundance of specific AKT isoforms in IBH-6 and T47D human breast cancer cell lines and showed that AKT1 promoted cell proliferation...

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Detalles Bibliográficos
Autores principales: Riggio, Marina, Perrone, María C., Polo, María L., Rodríguez, María J., May, María, Abba, Martín Carlos, Lanari, Claudia, Novaro, Virginia
Formato: Articulo
Lenguaje:Inglés
Publicado: 2017
Materias:
Ciencias Médicas
AKT1
AKT2
breast cancer
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/87340
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-87340
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
AKT1
AKT2
breast cancer
spellingShingle Ciencias Médicas
AKT1
AKT2
breast cancer
Riggio, Marina
Perrone, María C.
Polo, María L.
Rodríguez, María J.
May, María
Abba, Martín Carlos
Lanari, Claudia
Novaro, Virginia
AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
topic_facet Ciencias Médicas
AKT1
AKT2
breast cancer
description The purpose of this study was to elucidate the mechanisms associated with the specific effects of AKT1 and AKT2 isoforms in breast cancer progression. We modulated the abundance of specific AKT isoforms in IBH-6 and T47D human breast cancer cell lines and showed that AKT1 promoted cell proliferation, through S6 and cyclin D1 upregulation, but it inhibited cell migration and invasion through β1-integrin and focal adhesion kinase (FAK) downregulation. In contrast, AKT2 promoted cell migration and invasion through F-actin and vimentin induction. Thus, while overexpression of AKT1 promoted local tumor growth, downregulation of AKT1 or overexpression of AKT2 promoted peritumoral invasion and lung metastasis. Furthermore, we evaluated The Cancer Genome Atlas (TCGA) dataset for invasive breast carcinomas and found that increased AKT2 but not AKT1 mRNA levels correlated with a worse clinical outcome. We conclude that AKT isoforms play specific roles in different steps of breast cancer progression, with AKT1 involved in the local tumor growth and AKT2 involved in the distant tumor dissemination, having AKT2 a poorer prognostic value and consequently being a worthwhile target for therapy.
format Articulo
Articulo
author Riggio, Marina
Perrone, María C.
Polo, María L.
Rodríguez, María J.
May, María
Abba, Martín Carlos
Lanari, Claudia
Novaro, Virginia
author_facet Riggio, Marina
Perrone, María C.
Polo, María L.
Rodríguez, María J.
May, María
Abba, Martín Carlos
Lanari, Claudia
Novaro, Virginia
author_sort Riggio, Marina
title AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
title_short AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
title_full AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
title_fullStr AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
title_full_unstemmed AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
title_sort akt1 and akt2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
publishDate 2017
url http://sedici.unlp.edu.ar/handle/10915/87340
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