Melana Stella M, Nepomnaschy Irene, Sakalian Michael, Abbott Andrea, Hasa Jennifer, Holland James F, Pogo Beatriz G T
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Cancer Res. 2007 Sep 15;67(18):8960-5. doi: 10.1158/0008-5472.CAN-06-3892.
The association of human breast cancer with sequences similar to the mouse mammary tumor virus (MMTV) has been shown, but convincing evidence for the presence of viral particles in breast tumors has been lacking. We have described the complete proviral structure of a retrovirus in human breast cancer. This provirus, designated as human mammary tumor virus (HMTV), was 95% homologous to MMTV and revealed features of a replication-competent virus. We have therefore investigated the production of viral particles in primary cultures of human breast cancer (MSSM). Cells isolated from ascites or pleural effusions of patients with metastatic breast cancer contained viral sequences in their DNA, expressed Env protein, and showed retroviral particles by electron microscopy. Viral particles from culture media exhibited morphologic features of beta-retroviruses sedimenting at buoyant densities of 1.12 to 1.18 g/mL in sucrose gradients and showed reverse transcriptase activity. cDNA sequences from virion RNA were synthesized, amplified, and sequenced and all the virion genes were detected and 70% of the virion RNA was sequenced. The sequence homologies were, respectively, 85% to 95% compared with the MMTV and HMTV proviruses we have previously described. These results clearly show that breast cancer cells in primary cultures produced HMTV viral particles that are similar to the mouse virus and which may play a role in human breast cancer pathogenesis.
人类乳腺癌与类似于小鼠乳腺肿瘤病毒（MMTV）的序列之间的关联已得到证实，但在乳腺肿瘤中存在病毒颗粒的令人信服的证据一直缺乏。我们已经描述了人类乳腺癌中一种逆转录病毒的完整前病毒结构。这种前病毒被命名为人类乳腺肿瘤病毒（HMTV），与MMTV有95%的同源性，并显示出具有复制能力的病毒特征。因此，我们研究了人类乳腺癌原代培养物（MSSM）中病毒颗粒的产生。从转移性乳腺癌患者的腹水或胸腔积液中分离出的细胞，其DNA中含有病毒序列，表达Env蛋白，并通过电子显微镜显示出逆转录病毒颗粒。来自培养基的病毒颗粒呈现出β逆转录病毒的形态特征，在蔗糖梯度中以1.12至1.18 g/mL的浮力密度沉降，并显示出逆转录酶活性。合成、扩增并测序了病毒粒子RNA的cDNA序列，检测到了所有病毒粒子基因，并对70%的病毒粒子RNA进行了测序。与我们之前描述的MMTV和HMTV前病毒相比，序列同源性分别为85%至95%。这些结果清楚地表明，原代培养的乳腺癌细胞产生了与小鼠病毒相似的HMTV病毒颗粒，并且这些颗粒可能在人类乳腺癌发病机制中发挥作用。
