Research Papers:
Expression of ANO1/DOG1 is associated with shorter survival and progression of breast carcinomas
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Abstract
Jun Sang Bae1,*, Jeong Yeol Park2,*, See-Hyoung Park3, Sang Hoon Ha4, Ae Ri An1, Sang Jae Noh2, Keun Sang Kwon5, Sung Hoo Jung6, Ho Sung Park1, Myoung Jae Kang1 and Kyu Yun Jang1
1Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea
2Department of Forensic Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea
3Department of Bio and Chemical Engineering, Hongik University, Sejong, Republic of Korea
4Division of Biotechnology, Chonbuk National University, Iksan, Republic of Korea
5Department of Preventive Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea
6Department of Surgery, Chonbuk National University Medical School, Jeonju, Republic of Korea
*These authors contributed equally to this work
Correspondence to:
Kyu Yun Jang, email: [email protected]
Keywords: breast; carcinoma; ANO1; DOG1; prognosis
Received: August 24, 2017 Accepted: November 14, 2017 Published: December 09, 2017
ABSTRACT
The expression of ANO1 is considered to have diagnostic specificity for gastrointestinal stromal tumors. However, its function as a calcium-activated chloride channel suggests that the expression of ANO1 is not restricted to gastrointestinal stromal tumors. Recently, it has been reported that ANO1 has roles in the progression of human malignant tumors. However, the role of ANO1 in breast carcinoma has been controversial. Therefore, we investigated the expression of ANO1 in 139 breast carcinoma patients and the role of ANO1 in vitro. The immunohistochemical expression of ANO1 was significantly associated with the expression of β-catenin, cyclin D1, MMP9, snail, and E-cadherin. Especially, ANO1 expression was an independent indicator of poor prognosis of shorter overall survival and relapse-free survival of breast carcinoma patients by multivariate analysis. In MCF7 and MDA-MB-231 breast carcinoma cells, inhibition of ANO1 with T16Ainh-A01 or siRNA for ANO1 significantly suppressed the proliferation of cells. Knock-down of ANO1 with siRNA induced G0/G1 cell cycle arrest and significantly inhibited the invasiveness of breast carcinoma cells. Knock-down of ANO1 decreased the expression of β-catenin, cyclin D1, MMP9, snail, and N-cadherin, and increased the expression of E-cadherin. In conclusion, this study demonstrates that ANO1 expression is an indicator of poor prognosis of breast carcinoma patients and suggests that ANO1 might be a therapeutic target for breast carcinoma patients with ANO1-positive tumors and poor prognosis.
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