Akt/p27kip1 Pathway Is Not Involved in Human Insulinoma Tumorigenesis

Insulinomas are pancreatic neuroendocrine tumors (pNET), usually benign. Akt/p27kip1 is an intracellular pathway overexpressed in many pNET. There are no data regarding its expression in human insulinomas. We aimed to investigate the expression of Akt and p27kip1 in 24 human insulinomas and to compa...

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Main Authors: Adriana Graciela Díaz, Andrea Paes de Lima, Paula Garibaldi, Maria de los Milagros Rubio, Florencia García, Marta Kral, Oscar D. Bruno
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2018/7865072
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author Adriana Graciela Díaz
Andrea Paes de Lima
Paula Garibaldi
Maria de los Milagros Rubio
Florencia García
Marta Kral
Oscar D. Bruno
author_facet Adriana Graciela Díaz
Andrea Paes de Lima
Paula Garibaldi
Maria de los Milagros Rubio
Florencia García
Marta Kral
Oscar D. Bruno
author_sort Adriana Graciela Díaz
collection DOAJ
description Insulinomas are pancreatic neuroendocrine tumors (pNET), usually benign. Akt/p27kip1 is an intracellular pathway overexpressed in many pNET. There are no data regarding its expression in human insulinomas. We aimed to investigate the expression of Akt and p27kip1 in 24 human insulinomas and to compare them to their expression in normal surrounding islets. Staining was performed on embedded paraffin tissue using polyclonal antibodies against total Akt, p-Akt, p27kip1, and pp27kip1. p-Akt was the predominant form in insulinomas; they presented lower Akt and p-Akt expression than normal islets in 83.3% and 87.5% of tumors, respectively. p27kip1 and pp27kip1 were mainly cytoplasmic in both insulinomas and normal tissue. Cytoplasmic pp27kip1 staining was higher in insulinomas and surprisingly nearly half of the insulinomas also presented nuclear p27kip1 (p=0.029). No differences were observed in the subcellular localization of p27kip1 and activation of Akt between benign and malignant insulinomas. The low expression of Akt seen in insulinomas might explain the usual benign behavior of this type of pNET. Cytoplasmic p27kip1 in both insulinomas and normal islet cells could reflect the low rate of replication of beta cells, while nuclear p27kip1 would seem to indicate stabilization and nuclear anchoring of the cyclin D-Cdk4 complex. Our data seem to suggest that the Akt pathway is not involved in human insulinoma tumorigenesis.
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spelling doaj-art-4465925979e644d594632ddeafe65dcb2025-02-03T01:02:32ZengWileyInternational Journal of Endocrinology1687-83371687-83452018-01-01201810.1155/2018/78650727865072Akt/p27kip1 Pathway Is Not Involved in Human Insulinoma TumorigenesisAdriana Graciela Díaz0Andrea Paes de Lima1Paula Garibaldi2Maria de los Milagros Rubio3Florencia García4Marta Kral5Oscar D. Bruno6Division of Endocrinology, Hospital de Clínicas, Universidad de Buenos Aires, Buenos Aires, ArgentinaDepartment of Pathology, Hospital de Clínicas, Universidad de Buenos Aires, Buenos Aires, ArgentinaDivision of Endocrinology, Hospital de Clínicas, Universidad de Buenos Aires, Buenos Aires, ArgentinaDivision of Endocrinology, Hospital de Clínicas, Universidad de Buenos Aires, Buenos Aires, ArgentinaDepartment of Pathology, Hospital de Clínicas, Universidad de Buenos Aires, Buenos Aires, ArgentinaDivision of Endocrinology, Hospital de Clínicas, Universidad de Buenos Aires, Buenos Aires, ArgentinaDivision of Endocrinology, Hospital de Clínicas, Universidad de Buenos Aires, Buenos Aires, ArgentinaInsulinomas are pancreatic neuroendocrine tumors (pNET), usually benign. Akt/p27kip1 is an intracellular pathway overexpressed in many pNET. There are no data regarding its expression in human insulinomas. We aimed to investigate the expression of Akt and p27kip1 in 24 human insulinomas and to compare them to their expression in normal surrounding islets. Staining was performed on embedded paraffin tissue using polyclonal antibodies against total Akt, p-Akt, p27kip1, and pp27kip1. p-Akt was the predominant form in insulinomas; they presented lower Akt and p-Akt expression than normal islets in 83.3% and 87.5% of tumors, respectively. p27kip1 and pp27kip1 were mainly cytoplasmic in both insulinomas and normal tissue. Cytoplasmic pp27kip1 staining was higher in insulinomas and surprisingly nearly half of the insulinomas also presented nuclear p27kip1 (p=0.029). No differences were observed in the subcellular localization of p27kip1 and activation of Akt between benign and malignant insulinomas. The low expression of Akt seen in insulinomas might explain the usual benign behavior of this type of pNET. Cytoplasmic p27kip1 in both insulinomas and normal islet cells could reflect the low rate of replication of beta cells, while nuclear p27kip1 would seem to indicate stabilization and nuclear anchoring of the cyclin D-Cdk4 complex. Our data seem to suggest that the Akt pathway is not involved in human insulinoma tumorigenesis.http://dx.doi.org/10.1155/2018/7865072
spellingShingle Adriana Graciela Díaz
Andrea Paes de Lima
Paula Garibaldi
Maria de los Milagros Rubio
Florencia García
Marta Kral
Oscar D. Bruno
Akt/p27kip1 Pathway Is Not Involved in Human Insulinoma Tumorigenesis
International Journal of Endocrinology
title Akt/p27kip1 Pathway Is Not Involved in Human Insulinoma Tumorigenesis
title_full Akt/p27kip1 Pathway Is Not Involved in Human Insulinoma Tumorigenesis
title_fullStr Akt/p27kip1 Pathway Is Not Involved in Human Insulinoma Tumorigenesis
title_full_unstemmed Akt/p27kip1 Pathway Is Not Involved in Human Insulinoma Tumorigenesis
title_short Akt/p27kip1 Pathway Is Not Involved in Human Insulinoma Tumorigenesis
title_sort akt p27kip1 pathway is not involved in human insulinoma tumorigenesis
url http://dx.doi.org/10.1155/2018/7865072
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