Expression Of PRDM14 Research Articles

PRDM14 suppresses expression of differentiation marker genes in human embryonic stem cells

PRDM14 was identified by microarray analysis and was expressed in specifically undifferentiated human ES cells. PRDM14 protein is thought to regulate gene transcription in human ES cells, as it contains a PR domain, a subtype of the SET domain which catalyzes histone methylation. To analyze the function of PRDM14, we performed knock-down and forced expression of PRDM14 in human ES cells. Knock-down of PRDM14 by siRNA induced expression of early differentiation marker genes. Forced expression of PRDM14 suppressed expression of differentiation marker genes in the embryoid body. These results suggest that PRDM14 is involved in the maintenance of the self-renewal of human ES cells by suppression of gene expression.

Gene Amplification and Overexpression of PRDM14 in Breast Cancers

Several genes that encode PR (PRDI-BF1 and RIZ) domain proteins (PRDM) have been linked to human cancers. To explore the role of the PR domain family genes in breast carcinogenesis, we examined the expression profiles of 16 members of the PRDM gene family in a panel of breast cancer cell lines and primary breast cancer specimens using semiquantitative real-time PCR. We found that PRDM14 mRNA is overexpressed in about two thirds of breast cancers; moreover, immunohistochemical analysis showed that expression of PRDM14 protein is also up-regulated. Analysis of the gene copy number revealed that PRDM14 is a target of gene amplification on chromosome 8q13, which is a region where gene amplification has frequently been detected in various human tumors. Introduction of PRDM14 into cancer cells enhanced cell growth and reduced their sensitivity to chemotherapeutic drugs. Conversely, knockdown of PRDM14 by siRNA induced apoptosis in breast cancer cells and increased their sensitivity to chemotherapeutic drugs, suggesting that up-regulated expression of PRDM14 may play an important role in the proliferation of breast cancer cells. That little or no expression of PRDM14 is seen in noncancerous tissues suggests that PRDM14 could be an ideal therapeutic target for the treatment of breast cancer.