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人类恶性肿瘤中表皮生长因子受体(EGFr)表达概况:暴露于表皮生长因子(EGF)的影响及其对已建立的人类肿瘤细胞系的生物学作用

Profile of epidermal growth factor receptor (EGFr) expression in human malignancies: effects of exposure to EGF and its biological influence on established human tumour cell lines.

作者信息

Nouri A M, Thompson C, Cannell H, Symes M, Purkiss S, Amirghofran Z

机构信息

Uro/Oncology Research Unit, The Royal London Medical College, London E1 1BB, UK.

出版信息

Int J Mol Med. 2000 Oct;6(4):495-500. doi: 10.3892/ijmm.6.4.495.

DOI:10.3892/ijmm.6.4.495
PMID:10998445
Abstract

The aim of this study was to compare the profile of EGFr expression in transitional cell carcinoma of the bladder (TCC) and in oral squamous cell carcinoma (OSCC). In addition, to study the influence of EGF stimulation on the expression of major histocompatibility complex class I antigens, placental alkaline phosphatase (PLAP) as well as changes in tumour cell sensitivity to cisplatin using immunocytochemical staining, a colorimetric assay and SDS-gel electrophoresis. The results showed that: a) strong EGFr expression could be seen in 22/88 (27%) cases of TCCs. In oral tumours the values for non-invasive ameloblastoma and invasive OSCC were 4/25 (16%) and 30/41 (73%) respectively. b) EGFr expression in tumour cell lines paralleled that of tumour biopsies. The number of lines expressing high and low EGFr expression amongst TCCs were 4 and 4 and in OSCCs were 3 and 1 respectively. c) Exposure of tumour cell lines to EGF led to: i) an increase in EGFr expression (stimulatory indices SI, ranged from 1.06 to 2.58) for TCCs but a decrease in the case of OSCCs (SI ranged from 0.01 to 0.85). The corresponding SI values for class I antigens were 0.95-1.16 and 0.10-0.84. ii) A significant reduction in expression of PLAP by OSCC cell lines. iii) An increased susceptibility of OSCC cell lines to cisplatin by as much as 14% (p<0.001). These data demonstrated the overexpression of EGFr in a significant proportion of TCCs. As for oral tumours it depended on whether they were of an invasive or non-invasive type. In the invasive cases the majority overexpressed EGFr. The exposure of OSCC but not TCC tumour cells to EGF resulted in down regulation of EGFr and class I antigens. The expression of PLAP was also significantly reduced. Exposure of OSCC cells to EGF resulted in their increased susceptibility to cisplatin. The data supports the notion that the mitogenic activation of some tumour cells by EGF resulted in a reduction of their immune visibility, differentiation status and an increase in chemosensitivity.

摘要

本研究旨在比较膀胱移行细胞癌(TCC)和口腔鳞状细胞癌(OSCC)中表皮生长因子受体(EGFr)的表达情况。此外,还通过免疫细胞化学染色、比色测定法和十二烷基硫酸钠 - 凝胶电泳,研究表皮生长因子(EGF)刺激对主要组织相容性复合体I类抗原、胎盘碱性磷酸酶(PLAP)表达的影响以及肿瘤细胞对顺铂敏感性的变化。结果显示:a)在88例TCC病例中有22例(27%)可见EGFr强表达。在口腔肿瘤中,非侵袭性成釉细胞瘤和侵袭性OSCC的这一数值分别为4/25(16%)和30/41(73%)。b)肿瘤细胞系中EGFr的表达与肿瘤活检结果相似。TCC中高表达和低表达EGFr的细胞系数量分别为4个和4个,OSCC中分别为3个和1个。c)肿瘤细胞系暴露于EGF导致:i)TCC中EGFr表达增加(刺激指数SI,范围为1.06至2.58),而OSCC中则减少(SI范围为0.01至0.85)。I类抗原的相应SI值为0.95 - 1.16和0.10 - 0.84。ii)OSCC细胞系中PLAP的表达显著降低。iii)OSCC细胞系对顺铂的敏感性增加高达14%(p<0.001)。这些数据表明相当一部分TCC中存在EGFr的过表达。对于口腔肿瘤,这取决于它们是侵袭性还是非侵袭性类型。在侵袭性病例中,大多数EGFr过表达。OSCC而非TCC肿瘤细胞暴露于EGF导致EGFr和I类抗原下调。PLAP的表达也显著降低。OSCC细胞暴露于EGF导致其对顺铂的敏感性增加。这些数据支持这样一种观点,即EGF对某些肿瘤细胞的促有丝分裂激活导致其免疫可见性降低、分化状态改变以及化学敏感性增加。

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