ATP synthase ecto-α-subunit: A novel therapeutic target for breast cancer

Jian Pan; Li Chao Sun; Yan Fang Tao; Zhuan Zhou; Xiao Li Du; Liang Peng; Xing Feng; Jian Wang; Yi Ping Li; Ling Liu; Shui Yan Wu; Yan Lan Zhang; Shao Yan Hu; Wen Li Zhao; Xue Ming Zhu; Guo Liang Lou; Jian Ni

doi:10.1186/1479-5876-9-211

ATP synthase ecto-α-subunit: A novel therapeutic target for breast cancer

Jian Pan, Li Chao Sun, Yan Fang Tao, Zhuan Zhou, Xiao Li Du, Liang Peng, Xing Feng, Jian Wang, Yi Ping Li, Ling Liu, Shui Yan Wu, Yan Lan Zhang, Shao Yan Hu, Wen Li Zhao, Xue Ming Zhu, Guo Liang Lou^*, Jian Ni

^*Corresponding author for this work

Obstetrics and Gynecology

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

37 Scopus citations

Abstract

Background: Treatment failure for breast cancer is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in breast cancer cells in vitro and in vivo. Identification of new targets will facilitate the developmental pace of new techniques in screening and early diagnosis. Improved abilities to predict progression and metastasis, therapeutic response and toxicity will help to increase survival of breast cancer patients.Methods: Differential protein expression in two breast cancer cell lines, one with high and the other with low metastatic potential, was analyzed using two-dimensional liquid phase chromatographic fractionation (Proteome Lab PF 2D system) followed by matrix-assisted laser desorption/time-of-flight mass spectrometry (MALDI-TOF/MS).Results: Up regulation of α-subunit of ATP synthase was identified in high metastatic cells compared with low metastatic cells. Immunohistochemical analysis of 168 human breast cancer specimens on tissue microarrays revealed a high frequency of ATP synthase α-subunit expression in breast cancer (94.6%) compared to normal (21.2%) and atypical hyperplasia (23%) breast tissues. Levels of ATP synthase expression levels strongly correlated with large tumor size, poor tumor differentiation and advanced tumor stages (P < 0.05). ATP synthase α-subunit over-expression was detected on the surface of a highly invasive breast cancer cell line. An antibody against the ATP synthase α-subunit inhibited proliferation, migration and invasion in these breast cancer cells but not that of a non-tumor derived breast cell line.Conclusions: Over-expression of ATP synthase α-subunit may be involved in the progression and metastasis of breast cancer, perhaps representing a potential biomarker for diagnosis, prognosis and a therapeutic target for breast cancer. This finding of this study will help us to better understand the molecular mechanism of tumor metastasis and to improve the screening, diagnosis, as well as prognosis and/or prediction of responses to therapy for breast cancer.

Original language	English (US)
Article number	211
Journal	Journal of Translational Medicine
Volume	9
Issue number	1
DOIs	https://doi.org/10.1186/1479-5876-9-211
State	Published - Dec 8 2011

Funding

We thank Professor Zhi-hua Yang (Cancer Institute/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China) for kindly help. This work was supported by grants from the National Key Basic Research Program No. 2010CB933902, National Natural Science Foundation for youth No. 81100371, Natural Science Foundation of Jiangsu Province No. BK2011308, Universities Natural Science Foundation of Jiangsu Province No. 11KJB320014 and Talent’s subsidy project in science and education of department of public health of Suzhou City No. SWKQ1020. Medical innovation team and leading talent of jiangsu Province. No. LJ201126.

Keywords

Atp synthase α-subunit
Breast cancer
Monoclonal antibody
Tissue microarray
Two-dimensional liquid phase chromatographic fractionation

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

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

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10.1186/1479-5876-9-211

Cite this

@article{c234c2625b7046b5808195c852d2dbac,

title = "ATP synthase ecto-α-subunit: A novel therapeutic target for breast cancer",

abstract = "Background: Treatment failure for breast cancer is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in breast cancer cells in vitro and in vivo. Identification of new targets will facilitate the developmental pace of new techniques in screening and early diagnosis. Improved abilities to predict progression and metastasis, therapeutic response and toxicity will help to increase survival of breast cancer patients.Methods: Differential protein expression in two breast cancer cell lines, one with high and the other with low metastatic potential, was analyzed using two-dimensional liquid phase chromatographic fractionation (Proteome Lab PF 2D system) followed by matrix-assisted laser desorption/time-of-flight mass spectrometry (MALDI-TOF/MS).Results: Up regulation of α-subunit of ATP synthase was identified in high metastatic cells compared with low metastatic cells. Immunohistochemical analysis of 168 human breast cancer specimens on tissue microarrays revealed a high frequency of ATP synthase α-subunit expression in breast cancer (94.6%) compared to normal (21.2%) and atypical hyperplasia (23%) breast tissues. Levels of ATP synthase expression levels strongly correlated with large tumor size, poor tumor differentiation and advanced tumor stages (P < 0.05). ATP synthase α-subunit over-expression was detected on the surface of a highly invasive breast cancer cell line. An antibody against the ATP synthase α-subunit inhibited proliferation, migration and invasion in these breast cancer cells but not that of a non-tumor derived breast cell line.Conclusions: Over-expression of ATP synthase α-subunit may be involved in the progression and metastasis of breast cancer, perhaps representing a potential biomarker for diagnosis, prognosis and a therapeutic target for breast cancer. This finding of this study will help us to better understand the molecular mechanism of tumor metastasis and to improve the screening, diagnosis, as well as prognosis and/or prediction of responses to therapy for breast cancer.",

keywords = "Atp synthase α-subunit, Breast cancer, Monoclonal antibody, Tissue microarray, Two-dimensional liquid phase chromatographic fractionation",

author = "Jian Pan and Sun, {Li Chao} and Tao, {Yan Fang} and Zhuan Zhou and Du, {Xiao Li} and Liang Peng and Xing Feng and Jian Wang and Li, {Yi Ping} and Ling Liu and Wu, {Shui Yan} and Zhang, {Yan Lan} and Hu, {Shao Yan} and Zhao, {Wen Li} and Zhu, {Xue Ming} and Lou, {Guo Liang} and Jian Ni",

note = "Funding Information: We thank Professor Zhi-hua Yang (Cancer Institute/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China) for kindly help. This work was supported by grants from the National Key Basic Research Program No. 2010CB933902, National Natural Science Foundation for youth No. 81100371, Natural Science Foundation of Jiangsu Province No. BK2011308, Universities Natural Science Foundation of Jiangsu Province No. 11KJB320014 and Talent{\textquoteright}s subsidy project in science and education of department of public health of Suzhou City No. SWKQ1020. Medical innovation team and leading talent of jiangsu Province. No. LJ201126.",

year = "2011",

month = dec,

day = "8",

doi = "10.1186/1479-5876-9-211",

language = "English (US)",

volume = "9",

journal = "Journal of Translational Medicine",

issn = "1479-5876",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - ATP synthase ecto-α-subunit

T2 - A novel therapeutic target for breast cancer

AU - Pan, Jian

AU - Sun, Li Chao

AU - Tao, Yan Fang

AU - Zhou, Zhuan

AU - Du, Xiao Li

AU - Peng, Liang

AU - Feng, Xing

AU - Wang, Jian

AU - Li, Yi Ping

AU - Liu, Ling

AU - Wu, Shui Yan

AU - Zhang, Yan Lan

AU - Hu, Shao Yan

AU - Zhao, Wen Li

AU - Zhu, Xue Ming

AU - Lou, Guo Liang

AU - Ni, Jian

N1 - Funding Information: We thank Professor Zhi-hua Yang (Cancer Institute/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China) for kindly help. This work was supported by grants from the National Key Basic Research Program No. 2010CB933902, National Natural Science Foundation for youth No. 81100371, Natural Science Foundation of Jiangsu Province No. BK2011308, Universities Natural Science Foundation of Jiangsu Province No. 11KJB320014 and Talent’s subsidy project in science and education of department of public health of Suzhou City No. SWKQ1020. Medical innovation team and leading talent of jiangsu Province. No. LJ201126.

PY - 2011/12/8

Y1 - 2011/12/8

N2 - Background: Treatment failure for breast cancer is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in breast cancer cells in vitro and in vivo. Identification of new targets will facilitate the developmental pace of new techniques in screening and early diagnosis. Improved abilities to predict progression and metastasis, therapeutic response and toxicity will help to increase survival of breast cancer patients.Methods: Differential protein expression in two breast cancer cell lines, one with high and the other with low metastatic potential, was analyzed using two-dimensional liquid phase chromatographic fractionation (Proteome Lab PF 2D system) followed by matrix-assisted laser desorption/time-of-flight mass spectrometry (MALDI-TOF/MS).Results: Up regulation of α-subunit of ATP synthase was identified in high metastatic cells compared with low metastatic cells. Immunohistochemical analysis of 168 human breast cancer specimens on tissue microarrays revealed a high frequency of ATP synthase α-subunit expression in breast cancer (94.6%) compared to normal (21.2%) and atypical hyperplasia (23%) breast tissues. Levels of ATP synthase expression levels strongly correlated with large tumor size, poor tumor differentiation and advanced tumor stages (P < 0.05). ATP synthase α-subunit over-expression was detected on the surface of a highly invasive breast cancer cell line. An antibody against the ATP synthase α-subunit inhibited proliferation, migration and invasion in these breast cancer cells but not that of a non-tumor derived breast cell line.Conclusions: Over-expression of ATP synthase α-subunit may be involved in the progression and metastasis of breast cancer, perhaps representing a potential biomarker for diagnosis, prognosis and a therapeutic target for breast cancer. This finding of this study will help us to better understand the molecular mechanism of tumor metastasis and to improve the screening, diagnosis, as well as prognosis and/or prediction of responses to therapy for breast cancer.

AB - Background: Treatment failure for breast cancer is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in breast cancer cells in vitro and in vivo. Identification of new targets will facilitate the developmental pace of new techniques in screening and early diagnosis. Improved abilities to predict progression and metastasis, therapeutic response and toxicity will help to increase survival of breast cancer patients.Methods: Differential protein expression in two breast cancer cell lines, one with high and the other with low metastatic potential, was analyzed using two-dimensional liquid phase chromatographic fractionation (Proteome Lab PF 2D system) followed by matrix-assisted laser desorption/time-of-flight mass spectrometry (MALDI-TOF/MS).Results: Up regulation of α-subunit of ATP synthase was identified in high metastatic cells compared with low metastatic cells. Immunohistochemical analysis of 168 human breast cancer specimens on tissue microarrays revealed a high frequency of ATP synthase α-subunit expression in breast cancer (94.6%) compared to normal (21.2%) and atypical hyperplasia (23%) breast tissues. Levels of ATP synthase expression levels strongly correlated with large tumor size, poor tumor differentiation and advanced tumor stages (P < 0.05). ATP synthase α-subunit over-expression was detected on the surface of a highly invasive breast cancer cell line. An antibody against the ATP synthase α-subunit inhibited proliferation, migration and invasion in these breast cancer cells but not that of a non-tumor derived breast cell line.Conclusions: Over-expression of ATP synthase α-subunit may be involved in the progression and metastasis of breast cancer, perhaps representing a potential biomarker for diagnosis, prognosis and a therapeutic target for breast cancer. This finding of this study will help us to better understand the molecular mechanism of tumor metastasis and to improve the screening, diagnosis, as well as prognosis and/or prediction of responses to therapy for breast cancer.

KW - Atp synthase α-subunit

KW - Breast cancer

KW - Monoclonal antibody

KW - Tissue microarray

KW - Two-dimensional liquid phase chromatographic fractionation

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JO - Journal of Translational Medicine

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ER -

ATP synthase ecto-α-subunit: A novel therapeutic target for breast cancer

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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