Durgam V R, Tekmal R R
Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio 78284-7836.
Cancer Lett. 1994 Dec 9;87(2):179-86. doi: 10.1016/0304-3835(94)90220-8.
Our previous studies have resulted in the identification and cloning of int-5, a novel site of mouse mammary tumor virus (MMTV) integration, from BALB/c D2 precancerous hyperplastic alveolar nodules (HAN). This paper presents a detailed characterization of the int-5 locus from both D2 HAN and normal genome and expression of the unique gene from the MMTV integration site. Our results show that the cellular gene at the MMTV integration site in the int-5 locus is identical to the gene encoding aromatase (CYP19), a member of the cytochrome P-450 gene superfamily. MMTV is integrated within exon 10 in the 3' untranslated region of the aromatase gene. This gene (int-5/aromatase) is expressed in normal mammary gland and overexpressed in mammary tumors. These results suggest that the overexpression of this gene may be responsible for mammary tumorigenesis. This is the first demonstration of integration of MMTV in a cellular gene that plays a role in hormone-dependent breast cancers.
我们之前的研究已从BALB/c D2癌前增生性肺泡结节（HAN）中鉴定并克隆出int-5，这是小鼠乳腺肿瘤病毒（MMTV）整合的一个新位点。本文详细描述了来自D2 HAN和正常基因组的int-5基因座特征，以及MMTV整合位点独特基因的表达情况。我们的结果表明，int-5基因座中MMTV整合位点处的细胞基因与编码芳香化酶（CYP19）的基因相同，芳香化酶是细胞色素P-450基因超家族的成员之一。MMTV整合在芳香化酶基因3'非翻译区的第10外显子内。该基因（int-5/芳香化酶）在正常乳腺中表达，在乳腺肿瘤中过表达。这些结果表明，该基因的过表达可能与乳腺肿瘤发生有关。这是首次证明MMTV整合到一个在激素依赖性乳腺癌中起作用的细胞基因中。
