Histological evaluation of AMPK signalling in primary breast cancer

Sirwan M. Hadad; Lee Baker; Philip R. Quinlan; Katherine E. Robertson; Susan E. Bray; George Thomson; David Kellock; Lee B. Jordan; Colin A. Purdie; David G. Hardie; Stewart Fleming; Alastair M. Thompson

doi:10.1186/1471-2407-9-307

Histological evaluation of AMPK signalling in primary breast cancer

Sirwan M. Hadad, Lee Baker, Philip R. Quinlan, Katherine E. Robertson, Susan E. Bray, George Thomson, David Kellock, Lee B. Jordan, Colin A. Purdie, David G. Hardie, Stewart Fleming, Alastair M. Thompson

Research output: Contribution to journal › Article › peer-review

159 Citations (Scopus)

Abstract

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, ER alpha, 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, ERa, 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 reactivation could have therapeutic potential in breast cancer.

Original language	English
Article number	307
Pages (from-to)	-
Number of pages	9
Journal	BMC Cancer
Volume	9
DOIs	https://doi.org/10.1186/1471-2407-9-307
Publication status	Published - 1 Sept 2009

Keywords

ACTIVATED PROTEIN-KINASE
ACETYL-COA CARBOXYLASE
FATTY-ACID OXIDATION
CELLULAR-ENERGY
MAMMALIAN TARGET
SKELETAL-MUSCLE
MALONYL-COA
PHOSPHORYLATION
METFORMIN
CELLS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/1471-2407-9-307

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@article{4900c349099443f1a79cb380c6a4649e,

title = "Histological evaluation of AMPK signalling in primary breast cancer",

abstract = "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, ER alpha, 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, ERa, 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 reactivation could have therapeutic potential in breast cancer.",

keywords = "ACTIVATED PROTEIN-KINASE, ACETYL-COA CARBOXYLASE, FATTY-ACID OXIDATION, CELLULAR-ENERGY, MAMMALIAN TARGET, SKELETAL-MUSCLE, MALONYL-COA, PHOSPHORYLATION, METFORMIN, CELLS",

author = "Hadad, {Sirwan M.} and Lee Baker and Quinlan, {Philip R.} and Robertson, {Katherine E.} and Bray, {Susan E.} and George Thomson and David Kellock and Jordan, {Lee B.} and Purdie, {Colin A.} and Hardie, {David G.} and Stewart Fleming and Thompson, {Alastair M.}",

year = "2009",

month = sep,

day = "1",

doi = "10.1186/1471-2407-9-307",

language = "English",

volume = "9",

pages = "--",

journal = "BMC Cancer",

issn = "1471-2407",

publisher = "Springer Verlag",

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TY - JOUR

T1 - Histological evaluation of AMPK signalling in primary breast cancer

AU - Hadad, Sirwan M.

AU - Baker, Lee

AU - Quinlan, Philip R.

AU - Robertson, Katherine E.

AU - Bray, Susan E.

AU - Thomson, George

AU - Kellock, David

AU - Jordan, Lee B.

AU - Purdie, Colin A.

AU - Hardie, David G.

AU - Fleming, Stewart

AU - Thompson, Alastair M.

PY - 2009/9/1

Y1 - 2009/9/1

N2 - 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, ER alpha, 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, ERa, 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 reactivation could have therapeutic potential in breast cancer.

AB - 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, ER alpha, 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, ERa, 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 reactivation could have therapeutic potential in breast cancer.

KW - ACTIVATED PROTEIN-KINASE

KW - ACETYL-COA CARBOXYLASE

KW - FATTY-ACID OXIDATION

KW - CELLULAR-ENERGY

KW - MAMMALIAN TARGET

KW - SKELETAL-MUSCLE

KW - MALONYL-COA

KW - PHOSPHORYLATION

KW - METFORMIN

KW - CELLS

U2 - 10.1186/1471-2407-9-307

DO - 10.1186/1471-2407-9-307

M3 - Article

C2 - 19723334

SN - 1471-2407

VL - 9

SP - -

JO - BMC Cancer

JF - BMC Cancer

M1 - 307

ER -

Histological evaluation of AMPK signalling in primary breast cancer

Abstract

Keywords

UN SDGs

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