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.
Nishikawa
Noriko
N
Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University, Sapporo, Japan.
Toyota
Minoru
M
Suzuki
Hiromu
H
Honma
Toshio
T
Fujikane
Tomoko
T
Ohmura
Tousei
T
Nishidate
Toshihiko
T
Ohe-Toyota
Mutsumi
M
Maruyama
Reo
R
Sonoda
Tomoko
T
Sasaki
Yasushi
Y
Urano
Takeshi
T
Imai
Kohzoh
K
Hirata
Koichi
K
Tokino
Takashi
T
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005784:Gene Amplification; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection
D004268:DNA-Binding Proteins; C524724:PRDM14 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors