Yu Y, Xu F, Peng H, Fang X, Zhao S, Li Y, Cuevas B, Kuo W L, Gray J W, Siciliano M, Mills G B, Bast R C
Division of Medicine, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):214-9. doi: 10.1073/pnas.96.1.214.
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.
利用差异显示PCR技术，我们鉴定出一个与ras和rap具有高度同源性的基因[NOEY2，ARHI（由人类基因命名委员会命名）]，该基因在正常卵巢和乳腺上皮细胞中持续表达，但在卵巢癌和乳腺癌中不表达。通过转染重新表达NOEY2可抑制乳腺癌和卵巢癌细胞的克隆生长。生长抑制与细胞周期蛋白D1启动子活性的下调和p21（WAF1/CIP1）的诱导有关。为了确定导致癌症中NOEY2沉默的机制，我们发现该基因单等位基因表达且为母系印记。在41%的卵巢癌和乳腺癌中检测到该基因的杂合性缺失。在大多数杂合性缺失的癌症样本中，非印记的功能等位基因被删除。因此，NOEY2似乎是一个推定的印记肿瘤抑制基因，其功能在卵巢癌和乳腺癌中被废除。
