Tsao M S, Earp H S, Grisham J W
Cancer Res. 1985 Sep;45(9):4428-32.
The effect of epidermal growth factor (EGF) on the capacity for anchorage-independent growth of chemically treated rat hepatic epithelial cells has been investigated. We have performed the studies using 16 clonally derived cell strains which represented single cell-derived subpopulations of a heterogeneous rat hepatic epithelial cell line that had been tumorigenically transformed by 11 repeated treatments with N-methyl-N'-nitro-N-nitrosoguanidine. The results can be summarized as follows. (a) Secondary clonal subpopulations isolated from the colonies formed by these strains in soft agar subsequently and invariably acquired markedly enhanced colony-forming efficiencies as compared to their parental strains. (b) EGF could enhance or induce colony-forming ability in soft agar in all of these cell strains. (c) The magnitudes of enhancement of the colony-forming efficiencies by EGF in soft agar could not be correlated with the absolute EGF-binding capacity of these cell strains. (d) The enhancement or induction of the colony-forming ability by EGF was either reversible or irreversible, partially correlating with the expression of gamma-glutamyl transpeptidase activity by the strains. These findings indicate that the cellular capacity of liver epithelial cells to grow anchorage independently in soft agar medium can be graded according to the pattern of response of EGF induction of colony-forming ability. These grades may reflect the level of neoplastic transformation of these cells. Moreover during the multistep transformation of rat hepatic epithelial cells by a chemical carcinogen, EGF can be used to reveal the presence of altered cells which have acquired partial capacity for the anchor-age-independent growth property. This property may constitute an additional identifiable early step of the neoplastic transformation of these cells.
研究了表皮生长因子（EGF）对经化学处理的大鼠肝上皮细胞非锚定依赖性生长能力的影响。我们使用了16种克隆衍生的细胞株进行研究，这些细胞株代表了一个异质性大鼠肝上皮细胞系的单细胞衍生亚群，该细胞系经11次N-甲基-N'-硝基-N-亚硝基胍重复处理后发生了肿瘤转化。结果总结如下。（a）从这些细胞株在软琼脂中形成的集落中分离出的二级克隆亚群，与它们的亲代细胞株相比，随后总是获得显著提高的集落形成效率。（b）EGF能增强或诱导所有这些细胞株在软琼脂中的集落形成能力。（c）EGF在软琼脂中提高集落形成效率的幅度与这些细胞株的绝对EGF结合能力无关。（d）EGF对集落形成能力的增强或诱导要么是可逆的，要么是不可逆的，部分与这些细胞株γ-谷氨酰转肽酶活性的表达相关。这些发现表明，肝上皮细胞在软琼脂培养基中独立生长的细胞能力可以根据EGF诱导集落形成能力的反应模式进行分级。这些分级可能反映了这些细胞的肿瘤转化水平。此外，在大鼠肝上皮细胞经化学致癌物进行多步骤转化过程中，EGF可用于揭示已获得部分非锚定依赖性生长特性能力的改变细胞的存在。这种特性可能构成这些细胞肿瘤转化的另一个可识别的早期步骤。
