Hromas R, Morris J, Cornetta K, Berebitsky D, Davidson A, Sha M, Sledge G, Rauscher F
Department of Medicine, Walther Oncology Center, Indiana University Medical Center, Indianapolis 46202, USA.
Cancer Res. 1995 Aug 15;55(16):3610-4.
The zinc finger gene MZF-1 is preferentially expressed in primitive hematopoietic cells and plays an important role in regulating myelopoiesis. Regulators of development are potential targets for neoplastic transformation. This study investigated whether unregulated expression of MZF-1 could function as an oncogene. Retroviral transduction and subsequent overexpression of MZF-1 resulted in loss of contact inhibition, loss of substrate dependence, and more rapid cell cycling in NIH 3T3 cells. The MZF-1-transformed 3T3 cells formed aggressive tumors in athymic mice. Disruption of the tight lineage- and stage-specific regulation of MZF-1 can result in neoplastic transformation of embryonic fibroblasts. Therefore, MZF-1 represents a novel oncogene.
锌指基因MZF - 1在原始造血细胞中优先表达，并在调节骨髓生成中发挥重要作用。发育调节因子是肿瘤转化的潜在靶点。本研究调查了MZF - 1的失控表达是否可作为一种癌基因发挥作用。逆转录病毒转导及随后MZF - 1的过表达导致NIH 3T3细胞失去接触抑制、失去对底物的依赖性以及细胞周期加快。MZF - 1转化的3T3细胞在无胸腺小鼠中形成侵袭性肿瘤。MZF - 1严格的谱系和阶段特异性调节的破坏可导致胚胎成纤维细胞的肿瘤转化。因此，MZF - 1代表一种新的癌基因。
