Kocher O, Cheresh P, Brown L F, Lee S W
Departments of Pathology and Medicine, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA.
Clin Cancer Res. 1995 Oct;1(10):1209-15.
Using the differential display technique, selecting for genes up-regulated in renal cell carcinoma compared with normal renal parenchyma, we isolated a novel gene, designated DD96. As determined by in situ and Northern blot hybridization studies, DD96 is expressed only in rare normal epithelial cell populations, such as the proximal tubular epithelial cells of the kidney. However, it is expressed diffusely in malignant epithelial cells of the wide majority of renal cell carcinomas. In addition, DD96 is overexpressed markedly in various human carcinomas originating from the colon, breast, and lung, as well as in a number of cell lines derived from tumors of these organs compared with normal epithelial cell populations. Furthermore, the expression of DD96 is induced in immortalized breast ductal epithelial cell lines compared with normal breast ductal epithelial cells, and, in vivo, in premalignant conditions, such as adenoma of the colon and ductal carcinoma in situ of the breast. Sequence analysis of a complete cDNA clone isolated from a human kidney cDNA library revealed that DD96 encodes for a protein of approximately Mr 13,500. These results suggest that DD96 may play a role in the early events associated with malignant transformation; however, its function remains to be determined.
运用差异显示技术，筛选出与正常肾实质相比在肾细胞癌中上调的基因，我们分离出一个新基因，命名为DD96。通过原位杂交和Northern印迹杂交研究确定，DD96仅在罕见的正常上皮细胞群体中表达，如肾近端小管上皮细胞。然而，它在绝大多数肾细胞癌的恶性上皮细胞中广泛表达。此外，与正常上皮细胞群体相比，DD96在源自结肠、乳腺和肺的各种人类癌组织以及源自这些器官肿瘤的许多细胞系中均显著过表达。此外，与正常乳腺导管上皮细胞相比，DD96在永生化乳腺导管上皮细胞系中表达被诱导，并且在体内，在癌前病变如结肠腺瘤和乳腺原位导管癌中也有表达。从人肾cDNA文库中分离出的一个完整cDNA克隆的序列分析表明，DD96编码一种分子量约为13500的蛋白质。这些结果表明，DD96可能在与恶性转化相关的早期事件中起作用；然而，其功能仍有待确定。
