PCP4/PEP19 upregulates aromatase gene expression via CYP19A1 promoter I.1 in human breast cancer SK-BR-3 cells

// Kie Honjo 1, * , Taiji Hamada 2, * , Takuya Yoshimura 1 , Seiya Yokoyama 2 , Sohsuke Yamada 2, 3 , Yan-Qin Tan 4 , Lai K. Leung 4 , Norifumi Nakamura 1 , Yasuyo Ohi 5 , Michiyo Higashi 2 and Akihide Tanimoto 2 1 Department of Oral Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan 2 Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan 3 Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan 4 Faculty of Science, School of Life Sciences, Food and Nutritional Science Programme, The Chinese University of Hong Kong, Shatin, Hong Kong 5 Department of Pathology, Sagara Hospital, Social Medical Corporation Hakuaikai, Kagoshima, Japan * These authors have contributed equally to this work Correspondence to: Akihide Tanimoto, email: akit09@m3.kufm.kagoshima-u.ac.jp Keywords: PCP4/PEP19; breast cancer; aromatase; intratumoral heterogeneity Received: December 18, 2017      Accepted: May 23, 2018      Published: July 03, 2018 ABSTRACT The Purkinje cell protein 4/peptide 19 (PCP4/PEP19) is a novel breast cancer cell expressing peptide, originally found in the neural cells as an anti-apoptotic factor, could inhibit cell apoptosis and enhance cell migration and invasion in human breast cancer cell lines. The expression of PCP4/PEP19 is induced by estrogens in estrogen receptor-positive (ER + ) MCF-7 cells but also highly expressed in ER - SK-BR-3 cells. In this study, we investigated the effects of PCP4/PEP19 on aromatase gene expression in MCF-7 and SK-BR-3 human breast cancer cells. In SK-BR-3 cells but not in MCF-7 cells, PCP4/PEP19 knockdown by siRNA silencing decreased the aromatase expression in gene transcriptional level. When PCP4/PEP19 was overexpressed by CMV promoter-driven PCP4/PEP19 expressing plasmid transfection, aromatase gene transcription increased in SK-BR-3 cells. This aromatase gene transcription is mainly mediated through promoter region PI.1, which is usually active in the placental tissue but not in the breast cancer tissue. These results indicate a new function of PCP4/PEP19 that would enhance aromatase gene upregulation to supply estrogens in heterogeneous cancer microenvironment.