Anderson G R, Stoler D L
Institute for Molecular Genetics, Baylor College of Medicine, Houston, TX 77030-3498.
Bioessays. 1993 Apr;15(4):265-72. doi: 10.1002/bies.950150407.
Although VL30 retrotransposable elements have been associated with certain cancers for nearly twenty years, because of their expression in rodent malignancies and recombination into murine sarcoma viruses, their causative role, if any, in cancer has been uncertain and enigmatic. Recent findings suggest loss of normal transcriptional control of specific VL30 element expression may make a critical contribution to tumor progression at a step associated with malignant conversion, by bringing into play a cellular program normally involved in wound healing. This program, the fibroblast anoxic response system, includes an adaptation to glycolytic metabolism, secretion of metalloproteinases, and activation of an endonuclease. While appropriate for facilitating debris removal during wound healing, loss of control of this program in a cell which has already progressed to the benign neoplastic state has the potential to simultaneously produce the invasiveness and genomic instability characteristic of malignancy. Examination of tumors and tumor derived cell lines has confirmed that key aspects of this system are in fact activated in cancer.
尽管VL30逆转录转座元件与某些癌症相关已有近二十年，但由于它们在啮齿类动物恶性肿瘤中的表达以及重组到鼠肉瘤病毒中，它们在癌症中（如果有）的致病作用一直不确定且令人费解。最近的研究结果表明，特定VL30元件表达的正常转录控制的丧失可能通过激活通常参与伤口愈合的细胞程序，在与恶性转化相关的阶段对肿瘤进展做出关键贡献。这个程序，即成纤维细胞缺氧反应系统，包括对糖酵解代谢的适应、金属蛋白酶的分泌以及核酸内切酶的激活。虽然这在伤口愈合过程中有助于清除碎片是合适的，但在已经发展到良性肿瘤状态的细胞中，该程序失控有可能同时产生恶性肿瘤的侵袭性和基因组不稳定性特征。对肿瘤和肿瘤衍生细胞系的检查证实，该系统的关键方面实际上在癌症中被激活。
