NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas.
Using differential display PCR, we have identified a gene [NOEY2, ARHI (designation by the Human Gene Nomenclature Committee)] with high homology to ras and rap that is expressed consistently in normal ovarian and breast epithelial cells but not in ovarian and breast cancers. Reexpression of NOEY2 through transfection suppresses clonogenic growth of breast and ovarian cancer cells. Growth suppression was associated with down-regulation of the cyclin D1 promoter activity and induction of p21(WAF1/CIP1). In an effort to identify mechanisms leading to NOEY2 silencing in cancer, we found that the gene is expressed monoallelically and is imprinted maternally. Loss of heterozygosity of the gene was detected in 41% of ovarian and breast cancers. In most of cancer samples with loss of heterozygosity, the nonimprinted functional allele was deleted. Thus, NOEY2 appears to be a putative imprinted tumor suppressor gene whose function is abrogated in ovarian and breast cancers.
Yu
Y
Y
Division of Medicine, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Xu
F
F
Peng
H
H
Fang
X
X
Zhao
S
S
Li
Y
Y
Cuevas
B
B
Kuo
W L
WL
Gray
J W
JW
Siciliano
M
M
Mills
G B
GB
Bast
R C
RC
D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics; D002878:Chromosomes, Human, Pair 1; D019938:Cyclin D1 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D011905:Genes, ras; D018392:Genomic Imprinting; D018095:Germ-Line Mutation; D006131:Growth Inhibitors / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008969:Molecular Sequence Data; D009035:Mothers; D010051:Ovarian Neoplasms / Q000235:genetics*; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017386:Sequence Homology, Amino Acid; D020741:rho GTP-Binding Proteins
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C117386:DIRAS3 protein, human; D006131:Growth Inhibitors; D019938:Cyclin D1; D020741:rho GTP-Binding Proteins