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.
Highlights
Aromatase is an enzyme, catalyzing the last and ratelimiting step of biosynthesis for estrogens, and expressed in a wide variety of tissues including placenta, ovary, adipose and breast tissues [1]
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, PCP4/PEP19 is highly expressed in fetal bovine serum (FBS) supplemented culture medium, and the expression was decreased in culture with charcoalstripped FBS (CSFBS) supplemented medium, which showed still higher expression level than in MCF-7 cells
Summary
Aromatase is an enzyme, catalyzing the last and ratelimiting step of biosynthesis for estrogens, and expressed in a wide variety of tissues including placenta, ovary, adipose and breast tissues [1]. The understanding of regulation of aromatase gene expression in breast cancer tissues is important to develop a new therapeutic strategy. The aromatase is encoded by cytochrome P450, family 19, subfamily A, polypeptide 1 (CYP19A1) gene, and the expression is www.oncotarget.com regulated by several promoter regions classified promoters I and II (PI and PII), which are active in tissue-specific manner [7, 8]. The PI., PI.3, PI. and PII promoter regions are active in the breast cancer and the region PI. and PI. promoter works in the placenta [9], while the promoter regions PI., PI.4 and PII are active in the adipose tissues [10]
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