Watanabe T, Yamaguchi K, Takatsuki K, Osame M, Yoshida M
Department of Viral Oncology, Cancer Institute, Toshima-ku, Tokyo, Japan.
J Exp Med. 1990 Sep 1;172(3):759-65. doi: 10.1084/jem.172.3.759.
Adult T cell leukemia (ATL) is associated with human T cell leukemia virus type 1 (HTLV-1) infection, and almost all ATL patients have the complication of hypercalcemia. To understand the mechanism of the high incidence of hypercalcemia in ATL, we studied the expression of a parathyroid hormone-related protein (PTHrP) gene that has been proposed as a causative factor of hypercalcemia in some solid tumors. The polymerase chain reaction coupled with reverse transcription of mRNA was applied to RNA from peripheral blood mononuclear cells. Cells from all 13 ATL patients examined showed abundant expression of the PTHrP gene, while cells from uninfected normal subjects did not. Significant expression of PTHrP gene was also detected in HTLV-1 carriers without any symptoms and in patients with HTLV-1-associated myelopathy or tropical spastic paraparesis. PTHrP mRNA levels correlated with the number of infected cells that were estimated by the integrated HTLV-1 DNA. These results suggest that HTLV-1-infected cells are expressing the PTHrP gene. This concept was further supported by the finding that the HTLV-1 trans-activator, the tax gene product, caused trans-activation of the PTHrP gene promoter linked to the CAT gene. These observations might explain the general expression of the PTHrP gene in ATL patients and the high incidence of hypercalcemia in ATL.
成人T细胞白血病（ATL）与1型人类T细胞白血病病毒（HTLV-1）感染相关，几乎所有ATL患者都有高钙血症并发症。为了解ATL中高钙血症高发的机制，我们研究了甲状旁腺激素相关蛋白（PTHrP）基因的表达，该基因在一些实体瘤中被认为是高钙血症的致病因素。将聚合酶链反应与mRNA逆转录相结合应用于外周血单个核细胞的RNA。所有13例接受检查的ATL患者的细胞均显示PTHrP基因大量表达，而未感染的正常受试者的细胞则未表达。在无症状的HTLV-1携带者以及患有HTLV-1相关脊髓病或热带痉挛性截瘫的患者中也检测到了PTHrP基因的显著表达。PTHrP mRNA水平与通过整合的HTLV-1 DNA估计的感染细胞数量相关。这些结果表明，HTLV-1感染的细胞正在表达PTHrP基因。HTLV-1反式激活因子tax基因产物可导致与CAT基因相连的PTHrP基因启动子的反式激活，这一发现进一步支持了这一概念。这些观察结果可能解释了ATL患者中PTHrP基因的普遍表达以及ATL中高钙血症的高发。
