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Histological evaluation of AMPK signalling in primary breast cancer

BACKGROUND: AMP-activated protein kinase (AMPK) acts as a cellular fuel gauge that responds to energy stress by suppressing cell growth and biosynthetic processes, thus ensuring that energy-consuming processes proceed only if there are sufficient metabolic resources. Malfunction of the AMPK pathway...

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Autores principales: Hadad, Sirwan M, Baker, Lee, Quinlan, Philip R, Robertson, Katherine E, Bray, Susan E, Thomson, George, Kellock, David, Jordan, Lee B, Purdie, Colin A, Hardie, David G, Fleming, Stewart, Thompson, Alastair M
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744705/
https://www.ncbi.nlm.nih.gov/pubmed/19723334
http://dx.doi.org/10.1186/1471-2407-9-307
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author Hadad, Sirwan M
Baker, Lee
Quinlan, Philip R
Robertson, Katherine E
Bray, Susan E
Thomson, George
Kellock, David
Jordan, Lee B
Purdie, Colin A
Hardie, David G
Fleming, Stewart
Thompson, Alastair M
author_facet Hadad, Sirwan M
Baker, Lee
Quinlan, Philip R
Robertson, Katherine E
Bray, Susan E
Thomson, George
Kellock, David
Jordan, Lee B
Purdie, Colin A
Hardie, David G
Fleming, Stewart
Thompson, Alastair M
author_sort Hadad, Sirwan M
collection PubMed
description BACKGROUND: AMP-activated protein kinase (AMPK) acts as a cellular fuel gauge that responds to energy stress by suppressing cell growth and biosynthetic processes, thus ensuring that energy-consuming processes proceed only if there are sufficient metabolic resources. Malfunction of the AMPK pathway may allow cancer cells to undergo uncontrolled proliferation irrespective of their molecular energy levels. The aim of this study was to examine the state of AMPK phosphorylation histologically in primary breast cancer in relation to clinical and pathological parameters. METHODS: Immunohistochemistry was performed using antibodies to phospho-AMPK (pAMPK), phospho-Acetyl Co-A Carboxylase (pACC) an established target for AMPK, HER2, ERα, and Ki67 on Tissue Micro-Array (TMA) slides of two cohorts of 117 and 237 primary breast cancers. The quick score method was used for scoring and patterns of protein expression were compared with clinical and pathological data, including a minimum 5 years follow up. RESULTS: Reduced signal, compared with the strong expression in normal breast epithelium, using a pAMPK antibody was demonstrated in 101/113 (89.4%) and 217/236 (91.9%) of two cohorts of patients. pACC was significantly associated with pAMPK expression (p = 0.007 & p = 0.014 respectively). For both cohorts, reduced pAMPK signal was significantly associated with higher histological grade (p = 0.010 & p = 0.021 respectively) and axillary node metastasis (p = 0.061 & p = 0.039 respectively). No significant association was found between pAMPK and any of HER2, ERα, or Ki67 expression, disease-free survival or overall survival. CONCLUSION: This study extends in vitro evidence through immunohistochemistry to confirm that AMPK is dysfunctional in primary breast cancer. Reduced signalling via the AMPK pathway, and the inverse relationship with histological grade and axillary node metastasis, suggests that AMPK re-activation could have therapeutic potential in breast cancer.
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spelling pubmed-27447052009-09-16 Histological evaluation of AMPK signalling in primary breast cancer Hadad, Sirwan M Baker, Lee Quinlan, Philip R Robertson, Katherine E Bray, Susan E Thomson, George Kellock, David Jordan, Lee B Purdie, Colin A Hardie, David G Fleming, Stewart Thompson, Alastair M BMC Cancer Research Article BACKGROUND: AMP-activated protein kinase (AMPK) acts as a cellular fuel gauge that responds to energy stress by suppressing cell growth and biosynthetic processes, thus ensuring that energy-consuming processes proceed only if there are sufficient metabolic resources. Malfunction of the AMPK pathway may allow cancer cells to undergo uncontrolled proliferation irrespective of their molecular energy levels. The aim of this study was to examine the state of AMPK phosphorylation histologically in primary breast cancer in relation to clinical and pathological parameters. METHODS: Immunohistochemistry was performed using antibodies to phospho-AMPK (pAMPK), phospho-Acetyl Co-A Carboxylase (pACC) an established target for AMPK, HER2, ERα, and Ki67 on Tissue Micro-Array (TMA) slides of two cohorts of 117 and 237 primary breast cancers. The quick score method was used for scoring and patterns of protein expression were compared with clinical and pathological data, including a minimum 5 years follow up. RESULTS: Reduced signal, compared with the strong expression in normal breast epithelium, using a pAMPK antibody was demonstrated in 101/113 (89.4%) and 217/236 (91.9%) of two cohorts of patients. pACC was significantly associated with pAMPK expression (p = 0.007 & p = 0.014 respectively). For both cohorts, reduced pAMPK signal was significantly associated with higher histological grade (p = 0.010 & p = 0.021 respectively) and axillary node metastasis (p = 0.061 & p = 0.039 respectively). No significant association was found between pAMPK and any of HER2, ERα, or Ki67 expression, disease-free survival or overall survival. CONCLUSION: This study extends in vitro evidence through immunohistochemistry to confirm that AMPK is dysfunctional in primary breast cancer. Reduced signalling via the AMPK pathway, and the inverse relationship with histological grade and axillary node metastasis, suggests that AMPK re-activation could have therapeutic potential in breast cancer. BioMed Central 2009-09-01 /pmc/articles/PMC2744705/ /pubmed/19723334 http://dx.doi.org/10.1186/1471-2407-9-307 Text en Copyright ©2009 Hadad et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hadad, Sirwan M
Baker, Lee
Quinlan, Philip R
Robertson, Katherine E
Bray, Susan E
Thomson, George
Kellock, David
Jordan, Lee B
Purdie, Colin A
Hardie, David G
Fleming, Stewart
Thompson, Alastair M
Histological evaluation of AMPK signalling in primary breast cancer
title Histological evaluation of AMPK signalling in primary breast cancer
title_full Histological evaluation of AMPK signalling in primary breast cancer
title_fullStr Histological evaluation of AMPK signalling in primary breast cancer
title_full_unstemmed Histological evaluation of AMPK signalling in primary breast cancer
title_short Histological evaluation of AMPK signalling in primary breast cancer
title_sort histological evaluation of ampk signalling in primary breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744705/
https://www.ncbi.nlm.nih.gov/pubmed/19723334
http://dx.doi.org/10.1186/1471-2407-9-307
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