Hoffman A G, Burghardt R C, Tilley R, Auersperg N
Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station 77843.
Int J Cancer. 1993 Jul 9;54(5):828-38. doi: 10.1002/ijc.2910540518.
To investigate the cellular mechanisms of ovarian epithelial carcinogenesis, a series of progressively transformed rat ovarian surface epithelial (ROSE) cell lines were developed and studied. Transfection of primary ROSE cells and an immortalized ROSE line (ROSE 199) with the pSV3neo plasmid (SV40 T-antigen) yielded transformed lines which retained epithelial morphology. In vivo selection of these pSV3neo cell populations resulted in further phenotypic transformation. Transfection of ROSE 199 with pSV2neo/c-H-rasEJ (rasEJp21) resulted in a malignant line which appeared fibroblast-like and formed invasive sarcomas both in athymic mice and in immunocompetent rats. Gap junctional intercellular communication (GJIC) and cell-cell adhesion were studied in this series of ROSE lines. Both c-H-rasEJ-transformation and in vivo selection resulted in a significant reduction of GJIC between adjoining cells and a transition of in vitro migration as continuous epithelial sheets to the dissociation of individual cells. This apparent shift in cell adhesiveness was associated with reduced expression of the E-cadherin adhesion molecule. Our data suggest that neoplastic progression of the ovarian surface epithelium may be associated with concomitant reductions in GJIC, E-cadherin expression and functional adhesiveness.
为了研究卵巢上皮细胞癌变的细胞机制，我们建立并研究了一系列逐步转化的大鼠卵巢表面上皮（ROSE）细胞系。用pSV3neo质粒（SV40 T抗原）转染原代ROSE细胞和永生化ROSE系（ROSE 199），得到了保留上皮形态的转化细胞系。对这些pSV3neo细胞群体进行体内筛选，导致了进一步的表型转化。用pSV2neo/c-H-rasEJ（rasEJp21）转染ROSE 199，得到了一个恶性细胞系，该细胞系呈成纤维细胞样，在无胸腺小鼠和免疫活性大鼠中均形成侵袭性肉瘤。在这一系列ROSE细胞系中研究了间隙连接细胞间通讯（GJIC）和细胞间粘附。c-H-rasEJ转化和体内筛选均导致相邻细胞间GJIC显著降低，体外迁移从连续上皮片层转变为单个细胞解离。这种细胞粘附性的明显变化与E-钙粘蛋白粘附分子表达降低有关。我们的数据表明，卵巢表面上皮的肿瘤进展可能与GJIC、E-钙粘蛋白表达和功能粘附性的同时降低有关。
