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[表皮生长因子对人鳞状细胞癌细胞系诱导的细胞周期阻滞]

[Cell cycle arrest induced by epidermal growth factor on human squamous cell carcinoma cell lines].

作者信息

Kamata N, Enomoto S

机构信息

Second Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tokyo Medical and Dental University.

出版信息

Kokubyo Gakkai Zasshi. 1994 Sep;61(3):446-53. doi: 10.5357/koubyou.61.446.

Abstract

Although human squamous cell carcinoma (SCC) cell lines frequently contain an elevated number of epidermal growth factor (EGF) receptor accompanied with amplification of EGF receptor/c-erbB gene, it is well known that EGF inhibits the growth of these cells in culture at doses that stimulate the growth of epidermal keratinocytes and dermal fibroblasts. To study this growth inhibitory effect of EGF on the SCC cell lines, 3H-thymidine incorporation into DNA and cell cycle distribution were analyzed. In HSC-1 and NA cells, which contain the highest number of EGF receptor among these SCC cell lines, the inhibition of 3H-thymidine incorporation was apparent 2 to 4 hours after treatment with 100 ng/ml of EGF and reached more than 95% inhibition after 24 hours. Two-color cell cycle analysis using fluorescein isothiocyanate (FITC)-conjugated anti-Bromodeoxyuridine (BrdU) antibody and propidium iodide revealed that this inhibitory effect was due to cell cycle arrest not only in G1 but also in G2 phase. This effect was well correlated to the sensitivity to the growth inhibitory effect of EGF among the 4 SCC cell lines. These observations suggest that the SCC cells contain altered machineries which regulate the normal cell growth in both G1 and G2 phases, and the EGF affects these machineries via overexpressed its receptor.

摘要

虽然人类鳞状细胞癌(SCC)细胞系中表皮生长因子(EGF)受体数量常常增多,并伴有EGF受体/c-erbB基因的扩增,但众所周知,EGF在刺激表皮角质形成细胞和真皮成纤维细胞生长的剂量下,却能抑制这些细胞在培养中的生长。为研究EGF对SCC细胞系的这种生长抑制作用,分析了3H-胸腺嘧啶核苷掺入DNA的情况及细胞周期分布。在这些SCC细胞系中EGF受体数量最多的HSC-1和NA细胞中,用100 ng/ml EGF处理2至4小时后,3H-胸腺嘧啶核苷掺入的抑制作用就很明显,24小时后抑制率超过95%。使用异硫氰酸荧光素(FITC)偶联的抗溴脱氧尿苷(BrdU)抗体和碘化丙啶进行的双色细胞周期分析显示,这种抑制作用不仅是由于细胞周期停滞在G1期,还停滞在G2期。在4种SCC细胞系中,这种作用与对EGF生长抑制作用的敏感性密切相关。这些观察结果表明,SCC细胞含有改变的机制,这些机制在G1期和G2期调节正常细胞生长,而EGF通过其过表达的受体影响这些机制。

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