Inhibition by tumor-promoting phorbol esters of procollagen synthesis in promotable JB6 mouse epidermal cells.

Inhibition by tumor-promoting phorbol esters of procollagen synthesis in promotable JB6 mouse epidermal cells.
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促进肿瘤的佛波酯对促进 JB6 小鼠表皮细胞中原胶原合成的抑制。

DOI:
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发表时间:
1982
期刊:
Journal of the National Cancer Institute
影响因子:
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通讯作者:
N. Colburn
N. Colburn
中科院分区:
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文献类型:
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作者:
L. Dion;J. Bear;J. Bateman;L. D. De Luca;N. Colburn

文献摘要

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已经开发了JB 6小鼠表皮细胞系来研究体外肿瘤转化的促进作用。用12-O-十四烷酰佛波醇13-乙酸酯(TPA)或其他肿瘤促进剂处理JB 6细胞,导致JB 6细胞在裸鼠体内不可逆地获得致瘤性,并在软琼脂中非贴壁依赖性生长。如前所述,TPA治疗期间发生的生化反应之一是表观分子量为180,000的甘露糖标记糖蛋白减少超过75%。根据胶原酶和胃蛋白酶的敏感性,这种TPA敏感性糖蛋白现已被鉴定为前胶原前α 1(I)链。[3 H]脯氨酸标记也证明了150,000前胶原pro-alpha 2(I)组分的平行减少。两个nonphorbol启动子,mezerein和表皮生长因子,也积极减少前胶原的合成。JB 6的促进敏感性和促进抗性克隆衍生物显示出相似的胶原合成基础水平以及相似程度的TPA依赖性前胶原损失,表明胶原减少可能是必要的,但不足以产生促进反应。化学转化的小鼠表皮细胞系与paried nontransformants的比较表明,减少前胶原合成是一种稳定获得的表型变化,因此可能参与转化表型的维持及其诱导。
The JB6 mouse epidermal cell line has been developed to study promotion of neoplastic transformation in vitro. Treatment of JB6 cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) or other tumor promoters resulted in the irreversible acquisition by JB6 cells of tumorigenicity in nude mice and anchorage-independent growth in soft agar. As previously reported, one of the biochemical responses that occurs during TPA treatment is a greater than 75% reduction in a mannose-labeled glycoprotein with an apparent molecular weight of 180,000. This TPA-sensitive glycoprotein has now been identified on the basis of collagenase and pepsin sensitivity as procollagen pro-alpha 1(I) chain. [3H]proline labeling also demonstrated a parallel decrease in the 150,000 procollagen pro-alpha 2(I) component. Two nonphorbol promoters, mezerein and epidermal growth factor, were also active in decreasing procollagen synthesis. Promotion-sensitive and promotion-resistant clonal derivatives of JB6 showed similar basal levels of collagen synthesis as well as similar degrees of TPA-dependent procollagen loss indicating that the collagen decrease may be necessary but is not sufficient to produce the promotion response. Comparison of chemically transformed mouse epidermal cell lines with paried nontransformants suggests the reduced procollagen synthesis is a stably acquired phenotypic change and may therefore be involved in maintenance of the transformed phenotype as well as in its induction.