The novel imprinted carboxypeptidase A4 gene ( CPA4) in the 7q32 imprinting domain.
By a search for novel human imprinted genes in the vicinity of the imprinted gene MEST, at chromosome 7q32, we identified the carboxypeptidase A4 gene ( CPA4) in a gene cluster of the carboxypeptidase family, 200 kb centromeric to MEST. Because CPA4 was originally identified as a protein induced in a prostate cancer cell line (PC-3) by histone deacetylase inhibitors, and was located at the putative prostate cancer-aggressiveness locus at 7q32, we investigated its imprinting status in fetal tissues and in adult benign hypertrophic prostate (BPH). RT-PCR using four intragenic polymorphisms as markers showed that CPA4 was expressed preferentially from the maternal allele in the fetal heart, lung, liver, intestine, kidney, adrenal gland, and spleen, but not in the fetal brain. It was also preferentially expressed in the BPH. These findings support that CPA4 is imprinted and may become a strong candidate gene for prostate cancer-aggressiveness. As a Silver-Russell syndrome (SRS) locus has been proposed to be located to a region near MEST and to be involved in imprinting, CPA4 would have been a candidate gene for SRS. However, analysis of ten SRS patients revealed no mutations in CPA4.
Kayashima
Tomohiko
T
Department of Human Genetics, Nagasaki University School of Medicine, Japan.
Yamasaki
Kentaro
K
Yamada
Takahiro
T
Sakai
Hideki
H
Miwa
Nobutomo
N
Ohta
Tohru
T
Yoshiura
Koh-ichiro
K
Matsumoto
Naomichi
N
Nakane
Yoshibumi
Y
Kanetake
Hiroshi
H
Ishino
Fumitoshi
F
Niikawa
Norio
N
Kishino
Tatsuya
T
D000311:Adrenal Glands / Q000378:metabolism; D000328:Adult; D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D001921:Brain / Q000378:metabolism; D002268:Carboxypeptidases / Q000235:genetics*; D043422:Carboxypeptidases A; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D005333:Fetus; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007564:Japan; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009035:Mothers; D009206:Myocardium / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics; D011506:Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism
D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D011506:Proteins; C103637:mesoderm specific transcript protein; D002268:Carboxypeptidases; D043422:Carboxypeptidases A