Identification of Transcription Factor YY1 as a Regulator of a Prostate Cancer-Specific Pathway Using Proteomic Analysis.

Abstract

Prostate-specific antigen, a biomarker used to diagnose prostate cancer, exhibits poor sensitivity. Although previous studies have focused on identifying a new diagnostic biomarker, the molecules or networks identified in these studies are also present in other cancers, making it difficult to detect prostate cancer specifically. A unique characteristic of the prostate gland is the increased mitochondrial energy metabolism when normal prostate cells progress to cancer cells. Thus, we attempted to find a prostate cancer-specific signature present in this unique environment. Proteins that were differentially expressed between a prostate cell line and three prostate cancer cell lines were identified using proteomic analysis. Not surprisingly, the most prevalent proteins detected by network analysis of proteins that were up-regulated at least 1.2-fold in cancer cells, compared to that in normal prostate cells, were those involved in mitochondrial energy metabolism. In addition, we showed that Yin Yang 1 (YY1) was a major transcription factor involved in regulating energy metabolism. To determine whether YY1 regulates genes associated with mitochondrial energy metabolism in prostate cells, cells were subjected to quantitative polymerase chain reaction analysis in the presence or absence of the YY1 inhibitor NP-001. Notably, inhibition of YY1 resulted in reduced expression of genes related to the Krebs cycle and electron transport chain in prostate cancer cell lines. Based on this finding, we suggest that there is a tumor-specific signature that regulates mitochondrial energy metabolism in prostate cancer cells. This work provides a foundation for further work on identifying a means for the specific diagnosis of prostate cancer.