King B L, Carter D, Foellmer H G, Kacinski B M
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Am J Pathol. 1992 Jan;140(1):23-31.
In this communication, the authors summarize their characterization of eight ovarian adenocarcinoma-derived cell lines for level of neu gene amplification, expression of neu transcripts and protein, and intraperitoneal tumorigenicity in nude mice. Two of the eight cell lines in our study (SKOV3 and YAOVBIX1) exhibited five- to ninefold neu DNA sequence amplification, accompanied by up to 200-fold overexpression of transcripts and protein (p185). Both of these cell lines expressed a major approximately 7.5 kb neu-complementary transcript not previously reported in other neu-positive tumor cell lines. One pair of cell lines (YAOVBIX1 and YAOVBIX3), isolated from a single ovarian carcinoma patient's ascites sample differed dramatically in regard to level of neu gene amplification and expression. Immunohistochemical staining of the primary ovarian tumor from which these two lines were derived demonstrated populations of both neu-positive and neu-negative malignant epithelial cells. Seven of the eight ovarian carcinoma lines produced intra-abdominal tumors after intraperitoneal injection into nude mice, irrespective of level of neu gene expression. This study demonstrates tumor cell heterogeneity with regard to neu gene amplification and expression in an ovarian adenocarcinoma, reveals the overexpression of novel neu-complementary transcripts in two independently isolated ovarian adenocarcinoma cell lines, and suggests that neu gene expression is not required for intraperitoneal tumorigenicity of ovarian carcinoma xenografts in a nude mouse model system.
在本报告中,作者总结了他们对8种卵巢腺癌衍生细胞系的特性研究,包括neu基因扩增水平、neu转录本和蛋白的表达,以及在裸鼠体内的腹腔致瘤性。我们研究中的8种细胞系中有2种(SKOV3和YAOVBIX1)表现出5至9倍的neu DNA序列扩增,同时转录本和蛋白(p185)的表达高达200倍。这两种细胞系均表达一种主要的约7.5 kb的neu互补转录本,此前在其他neu阳性肿瘤细胞系中未见报道。从一名卵巢癌患者的腹水样本中分离出的一对细胞系(YAOVBIX1和YAOVBIX3)在neu基因扩增和表达水平上存在显著差异。对这两个细胞系来源的原发性卵巢肿瘤进行免疫组织化学染色,显示出neu阳性和neu阴性恶性上皮细胞群体。8种卵巢癌细胞系中有7种在腹腔注射到裸鼠体内后产生了腹腔内肿瘤,与neu基因表达水平无关。本研究证明了卵巢腺癌中neu基因扩增和表达方面的肿瘤细胞异质性,揭示了两种独立分离的卵巢腺癌细胞系中新型neu互补转录本的过表达,并表明在裸鼠模型系统中,neu基因表达对于卵巢癌异种移植物的腹腔致瘤性并非必需。