Mintz B, Klein-Szanto A J
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111.
Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11421-5. doi: 10.1073/pnas.89.23.11421.
Eye tumors of the retinal pigment epithelium (RPE) have been thought generally to be benign, whereas choroidal ones are malignant. To test this assumption in mice, the W/Wv (Kit) mutant genotype was introduced into melanoma-prone transgenic mice whose recombinant simian virus 40 transforming sequences are specifically expressed in pigment cells. W/Wv causes programmed death of neural crest-derived pigment cells, including choroidal ones, but leaves intact the brain-derived pigment cells, such as those in the RPE. Dysplastic cells arose in the RPE, contiguous with frank melanotic neoplasms. Invasion of the optic nerve, and tumor growth outside the orbit, attested to the malignancy of these RPE-derived melanomas. The widespread melanosis previously seen in mice with this transgene was absent when W/Wv was added, thus validating its chief origin from neural crest cells.
视网膜色素上皮（RPE）的眼部肿瘤一般被认为是良性的，而脉络膜的则是恶性的。为了在小鼠中验证这一假设，将W/Wv（Kit）突变基因型导入易患黑色素瘤的转基因小鼠中，其重组猿猴病毒40转化序列在色素细胞中特异性表达。W/Wv导致神经嵴来源的色素细胞，包括脉络膜色素细胞程序性死亡，但使脑来源的色素细胞，如RPE中的色素细胞保持完整。发育异常的细胞出现在RPE中，与明显的黑素瘤相邻。视神经的侵袭以及眼眶外的肿瘤生长，证明了这些RPE来源的黑色素瘤具有恶性特征。当加入W/Wv时，以前在带有这种转基因的小鼠中看到的广泛黑色素沉着消失了，从而证实其主要起源于神经嵴细胞。
