Progressive abrogation of TGF‐β‐1 and EGF growth control is associated with tumour progression in ras‐transfected human keratinocytes
Progressive abrogation of TGF‐β‐1 and EGF growth control is associated with tumour progression in ras‐transfected human keratinocytes
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TGF-β-1 和 EGF 生长控制的逐渐废除与 ras 转染的人角质形成细胞中的肿瘤进展相关
DOI：
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
S. Prime
中科院分区：
文献类型：
--
作者：
S. Game;A. Huelsen;V. Patel;M. Donnelly;W. Yeudall;A. Stone;N. Fusenig;S. Prime
本研究检测了不同转化阶段的人角质形成细胞对外源性TGF-β 1和EGF的反应及其受体和生长因子表达。自发永生化HaCaT细胞系和c-Ha-ras转染克隆（1-6、1-7、11-3、11-4）的细胞在移植至无胸腺小鼠时表现出不同的致瘤潜力。HaCaT-和1-6细胞无致瘤性，1-7细胞形成持续性表皮囊肿（良性肿瘤），11 - 3和11 - 4细胞发展为浸润性鳞状细胞癌。TGF-β 1以剂量依赖性方式抑制胸苷摄取，反应进行性降低与恶性潜能增加相关（HaCaT > 1-6 > 1-7 = 11 - 4）。HaCaT-细胞和ras-克隆表达TGF-β I mRNA的水平相似，但恶性潜能增加的细胞向培养基中分泌的受体结合TGF-β明显较少（HaCaT > 1-6 = 1-7 > 11 - 3 > 11 - 4）。虽然ras转染细胞表达的TGF-β受体比HaCaT细胞少，但4种转染细胞克隆之间的TGF-β受体数量或亲和力几乎没有差异。TGF-β受体类型也是如此，但恶性克隆11 - 3和11 - 4表达的11型受体水平较低。当研究HaCaT和ras转染细胞对外源性EGF的反应时，细胞是难治性的（1-7，11 - 4），部分刺激的（1-6）或完全刺激的（HaCaT）。恶性潜能增加的细胞产生的内源性TGF-α数量增加（11 - 4 = 11 - 3 > 1-7 = 1-6 > HaCaT）。所有致瘤性ras克隆表达的mRNA水平均高于HaCaT细胞。Ras转染的克隆表达的高亲和力和低亲和力EGF受体比HaCaT细胞少，高亲和力EGF受体数量增加的趋势与恶性潜能增加有关（11 - 4 = 11 - 3 > 1-7 > 1-6），但这些变化与受体亲和力的进行性降低有关。结果表明，转染c-Ha-ras的人表皮角质形成细胞中的肿瘤进展与TGF-β 1和EGF生长控制的逐渐消除相关。他们认为，与上皮肿瘤进展的晚期阶段相关的自主生长潜力增加可以使用TGF-β和EGF的细胞谱更密切地定义。© 1992 Wiley利斯公司
This study examined the response of human keratinocytes in different stages of transformation to exogenous TGF‐β 1 and EGF as well as their receptor and growth‐factor expression. Cells of the spontaneously immortalized HaCaT cell line and c‐Ha‐ras transfected clones (1–6, 1–7, 11–3, 11–4) exhibited different tumorigenic potentials when transplanted to athymic mice. HaCaT‐ and 1–6 cells were non‐tumorigenic, 1–7 cells formed persisting epidermal cysts (benign tumours) and 11‐3 and 11‐4 cells developed into invasive squamous‐cell carcinomas. TGF‐β 1 inhibited thymidine uptake in a dose‐dependent manner, a progressive decrease in response being associated with an increasing malignant potential (HaCaT > 1–6 > 1–7 = 11‐4). HaCaT‐cells and ras‐clones expressed TGF‐β I mRNA at similar levels, but cells of increasing malignant potential secreted markedly less receptor‐binding TGF‐P (HaCaT > 1–6 = 1–7 > 11‐3 > 11‐4) into the culture medium. Whilst ras‐transfected cells expressed fewer TGF‐P receptors than HaCaT cells, there was little difference between TGF‐p receptor number or affinity between the 4 transfected cell clones. The same was true for the TGF‐p receptor types, but Type‐11 receptors were expressed at lower levels by the malignant clones 11‐3 and 11‐4. When HaCaT and ras‐transfected cells were investigated for their response to exogenous EGF, cells were refractory (1–7, 11‐4), partially stimulated (1–6) or fully stimulated (HaCaT). Cells with increasing malignant potential produced increasing amounts of endogenous TGF‐α (11‐4 = 11‐3 > 1–7 = 1–6 > HaCaT). All tumorigenic ras clones expressed higher mRNA levels than HaCaT‐cells. Ras‐transfected clones expressed fewer high‐ and low‐affinity EGF receptors than HaCaT cells with a tendency toward increased numbers of high‐affinity EGF receptors associated with increasing malignant potential (11‐4 = 11‐3 > 1–7 > 1–6) but these changes were associated with a progressive decrease in receptor affinity. The results indicate that tumour progression in human epidermal keratinocytes transfected with c‐Ha‐ras is associated with a progressive abrogation of TGF‐β 1 and EGF growth control. They suggest that the increased autonomous growth potential associated with advanced stages of epithelial tumour progression can be defined more closely using a cellular profile of TGF‐β and EGF. © 1992 Wiley‐Liss, Inc.
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影响因子：
56.9
作者：
HEIMARK, RL;TWARDZIK, DR;SCHWARTZ, SM
通讯作者：
SCHWARTZ, SM
通过多种转导途径调节转化生长因子β1的作用：G蛋白依赖性和非依赖性信号传导的证据。
影响因子：
11.2
作者：
Howe,PH;Bascom,CC;Cunningham,MR;Leof,EB
通讯作者：
Leof,EB
通过 TGF-β 受体 I 和 II 缺陷的细胞之间的基因互补，恢复对转化生长因子-β (TGF-β) 的反应性。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Laiho,M;Weis,FM;Boyd,FT;Ignotz,RA;Massagué,J
通讯作者：
Massagué,J
TGF-β 抗性细胞突变体中 I 型和 II 型转化生长因子 (TGF)-β 受体同时丧失，表明两种受体类型都参与信号转导。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Laiho,M;Weis,MB;Massagué,J
通讯作者：
Massagué,J
将 Ha-ras 癌基因引入大鼠肝上皮细胞和实质肝细胞可赋予对 TGF-β 生长抑制作用的抵抗力。
影响因子：
8
作者：
Houck,KA;Michalopoulos,GK;Strom,SC
通讯作者：
Strom,SC