Shiramizu M, Katsuoka Y, Grodberg J, Koury S T, Fletcher J A, Davis K L, Sytkowski A J
Tokai University School of Medicine, Department of Urology, Kanagawa, Japan.
Exp Cell Res. 1994 Dec;215(2):249-56. doi: 10.1006/excr.1994.1340.
The paraneoplastic syndrome of erythrocytosis is associated with a variety of neoplasms including renal adenocarcinoma, cerebellar hemangioma, and hepatoma. We now report the characterization of the biological and molecular features of an erythropoietin-secreting human renal adenocarcinoma, designated RCCEp+. Serial transplantation of the tumor in athymic mice resulted in a dramatic increase in hematocrit and serum erythropoietin concentration. Growth in vitro was accompanied by a constant rate of erythropoietin secretion. Karyotype analysis demonstrated several unusual features, including the absence of 3p deletions and near tetraploidy. Erythropoietin mRNA was demonstrated by Northern blot both in freshly excised tumor and in tumor cells growing in vitro. Erythropoietin secretion was constitutive and was not induced either by cobalt or hypoxia. Southern blot analysis revealed no rearrangement of the erythropoietin gene in the tumor. Interestingly, in situ hybridization demonstrated erythropoietin mRNA in only a small population of the tumor cells. Further studies of RCCEp+ should prove useful in elucidating the molecular basis for this paraneoplastic syndrome.
红细胞增多症的副肿瘤综合征与多种肿瘤有关，包括肾腺癌、小脑血管瘤和肝癌。我们现在报告一种分泌促红细胞生成素的人类肾腺癌（命名为RCCEp+）的生物学和分子特征。将该肿瘤在无胸腺小鼠中连续传代移植导致血细胞比容和血清促红细胞生成素浓度显著增加。体外生长伴随着促红细胞生成素的持续分泌。核型分析显示了几个异常特征，包括无3p缺失和接近四倍体。通过Northern印迹法在新鲜切除的肿瘤和体外生长的肿瘤细胞中均检测到促红细胞生成素mRNA。促红细胞生成素的分泌是组成性的，不受钴或缺氧诱导。Southern印迹分析显示肿瘤中促红细胞生成素基因无重排。有趣的是，原位杂交显示仅在一小部分肿瘤细胞中存在促红细胞生成素mRNA。对RCCEp+的进一步研究将有助于阐明这种副肿瘤综合征的分子基础。
