Rubin A L, Arnstein P, Rubin H
Virus Laboratory, University of California, Berkeley 94720.
Proc Natl Acad Sci U S A. 1990 Dec;87(24):10005-9. doi: 10.1073/pnas.87.24.10005.
NIH 3T3 cells undergo morphological transformation in response to conditions of constrained growth, such as occur in low serum concentrations or at confluence. Transformation is expressed in a small fraction of the cells by the appearance of discrete foci of multiplying cells on a confluent monolayer of quiescent cells. We isolated and expanded cell populations from three dense and three light foci. Cells from each of these populations efficiently reproduced foci of the same morphotype when grown on a background of nontransformed NIH 3T3 cells. Using cultures derived from one of the dense foci (subline D/2), we found that the number of focus-forming units was stable and the cells remained tumorigenic when they were subjected to repeated thrice-weekly passage in 2% calf serum. However, equivalent passage in 10% calf serum eventually rendered the cells incapable of both focus production and tumor formation. The results show that the capacity to produce tumors as well as morphological transformation are produced as a response to physiological constraints of growth and/or metabolism in the absence of carcinogens and that both properties can be reversed by lifting the constraints. This behavior is typical of an adaptational response and, taken together with other supporting evidence, shows that tumorigenesis does not require conventional genetic alteration.
NIH 3T3细胞在诸如低血清浓度或汇合状态等生长受限条件下会发生形态转化。在静止细胞的汇合单层上，增殖细胞的离散集落出现表明一小部分细胞发生了转化。我们从三个密集集落和三个浅色集落中分离并扩增了细胞群体。当在未转化的NIH 3T3细胞背景上生长时，这些群体中的每个群体的细胞都能高效地重现相同形态类型的集落。使用来自一个密集集落（亚系D/2）的培养物，我们发现集落形成单位的数量是稳定的，并且当它们在2%小牛血清中每周三次重复传代时，细胞仍具有致瘤性。然而，在10%小牛血清中进行同等传代最终使细胞既不能形成集落也不能形成肿瘤。结果表明，在没有致癌物的情况下，产生肿瘤的能力以及形态转化是对生长和/或代谢的生理限制的一种反应，并且通过解除限制这两种特性都可以逆转。这种行为是适应性反应的典型特征，与其他支持证据一起表明肿瘤发生不需要传统的基因改变。
