Griep A E, Westphal H
Department of Oncology, McArdle Laboratory, University of Wisconsin-Madison 53706.
New Biol. 1990 Aug;2(8):727-38.
Expression of the immortalizing oncogene polyoma large T antigen (PyLT) in the lens of transgenic mice impairs fiber cell differentiation but does not induce hyperplasia or tumor development. To examine this phenotype further, we studied the expression of the lens-specific crystallin genes in normal mice and mice of the transgenic alpha PyLT1 lineage. Immunochemical analyses showed that the spatial pattern of expression of alpha, beta, and gamma crystallins was abnormal in lenses from alpha PyLT1 mice, and that abnormally differentiated lens cells expressed beta and gamma crystallins. We also found that the levels of expression of the crystallin proteins in the transgenic mice were reduced compared to those in normal mice. In vitro, epithelial lens cells from alpha PyLT1 mice expressed not only PyLT and alpha crystallins, but also beta and gamma crystallins, which occur specifically in differentiated cells. Yet, despite their nonproliferative nature in vivo and their expression of differentiated lens cell markers, lens cells from alpha PyLT1 mice proliferated indefinitely in vitro. The growth of the alpha PyLT1 lens cells in culture was inhibited by treatment with exogenous basic fibroblast growth factor, which is thought to be involved in growth and differentiation of lens cells in vivo. These results suggest that factors in the microenvironment of the eye may be important in the process of tumor formation in vivo.
永生化癌基因多瘤大T抗原（PyLT）在转基因小鼠晶状体中的表达会损害纤维细胞分化，但不会诱导增生或肿瘤形成。为了进一步研究这种表型，我们研究了正常小鼠和转基因αPyLT1品系小鼠晶状体特异性晶状体蛋白基因的表达。免疫化学分析表明，αPyLT1小鼠晶状体中α、β和γ晶状体蛋白的表达空间模式异常，且异常分化的晶状体细胞表达β和γ晶状体蛋白。我们还发现，与正常小鼠相比，转基因小鼠中晶状体蛋白的表达水平降低。在体外，αPyLT1小鼠的晶状体上皮细胞不仅表达PyLT和α晶状体蛋白，还表达特异性存在于分化细胞中的β和γ晶状体蛋白。然而，尽管αPyLT1小鼠的晶状体细胞在体内具有非增殖特性且表达分化的晶状体细胞标志物，但它们在体外却能无限增殖。用外源性碱性成纤维细胞生长因子处理可抑制培养的αPyLT1晶状体细胞的生长，碱性成纤维细胞生长因子被认为参与体内晶状体细胞的生长和分化。这些结果表明，眼部微环境中的因素在体内肿瘤形成过程中可能很重要。
