Portella G, Liddell J, Crombie R, Haddow S, Clarke M, Stoler A B, Balmain A
Beatson Institute for Cancer Research, Glasgow, UK.
Invasion Metastasis. 1994;14(1-6):7-16.
The ultimate stage of carcinogenesis in both human and mouse epithelial cells is the ability to invade surrounding tissues and metastasize to distant sites. In mouse skin tumours, the development of the invasive, spindle cell phenotype is associated with an imbalance of alleles on mouse chromosome 7, including the H-ras gene. In previous work, we have described clonally related squamous and spindle cell lines from the same primary tumour which differed substantially in morphology and behaviour, but showed the same series of mutations in H-ras and p53 genes. One of the events which takes place during this transition is disruption of cell-cell contacts, possibly due to the induced expression of metalloproteinases such as stromelysin-1 and disappearance of the cell adhesion molecule E-cadherin. Parallel studies using somatic cell hybrids have shown that the spindle cell phenotype is recessive in hybrids between squamous and spindle cells. We propose that an important epidermal differentiation-controlling gene is lost during the spindle cell transition.
在人类和小鼠上皮细胞中，致癌作用的最终阶段是侵入周围组织并转移至远处部位的能力。在小鼠皮肤肿瘤中，侵袭性梭形细胞表型的发展与小鼠7号染色体上包括H-ras基因在内的等位基因失衡有关。在之前的研究中，我们描述了来自同一原发性肿瘤的克隆相关的鳞状细胞系和梭形细胞系，它们在形态和行为上有很大差异，但在H-ras和p53基因中显示出相同系列的突变。在这种转变过程中发生的一个事件是细胞间接触的破坏，这可能是由于诸如基质溶解素-1等金属蛋白酶的诱导表达以及细胞粘附分子E-钙粘蛋白的消失所致。使用体细胞杂种的平行研究表明，梭形细胞表型在鳞状细胞和梭形细胞之间的杂种中是隐性的。我们提出，在梭形细胞转变过程中一个重要的表皮分化控制基因丢失了。
