PCP4/PEP19 upregulates aromatase gene expression via CYP19A1 promoter I.1 in human breast cancer SK-BR-3 cells
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Kie Honjo1,*, Taiji Hamada2,*, Takuya Yoshimura1, Seiya Yokoyama2, Sohsuke Yamada2,3, Yan-Qin Tan4, Lai K. Leung4, Norifumi Nakamura1, Yasuyo Ohi5, Michiyo Higashi2 and Akihide Tanimoto2
1Department of Oral Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
2Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
3Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa, Japan
4Faculty of Science, School of Life Sciences, Food and Nutritional Science Programme, The Chinese University of Hong Kong, Shatin, Hong Kong
5Department of Pathology, Sagara Hospital, Social Medical Corporation Hakuaikai, Kagoshima, Japan
*These authors have contributed equally to this work
Akihide Tanimoto, email: firstname.lastname@example.org
Keywords: PCP4/PEP19; breast cancer; aromatase; intratumoral heterogeneity
Received: December 18, 2017 Accepted: May 23, 2018 Published: July 03, 2018
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.
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