The role of transforming growth factor alpha in the enterochromaffin-like cell tumor autonomy in an African rodent mastomys.
The role of transforming growth factor alpha in the enterochromaffin-like cell tumor autonomy in an African rodent mastomys.
复制标题
转化生长因子α在非洲啮齿动物乳腺瘤肠嗜铬样细胞肿瘤自主性中的作用。
DOI：
10.1053/gast.1996.v111.pm8898635
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发表时间：
1996
期刊：
影响因子：
29.4
通讯作者：
Chinery,R
中科院分区：
文献类型：
--
作者：
Tang,LH;Modlin,IM;Lawton,GP;Kidd,M;Chinery,R
背景与目的胃类癌是由肠嗜铬样细胞（ECL）增生演变而来的，常伴有高pH和高胃泌素血症.乳鼠属物种表现出胃类癌形成的遗传倾向，酸抑制诱导的高胃泌素血症可以加速这种倾向。虽然胃泌素在ECL细胞转化的起始中是关键的，但参与肿瘤自主性演变的其他生长因子的作用尚未确定。本研究的目的是评估转化生长因子（TGF）α在ECL细胞transformation.METHODSMastomys的调节中的作用，口服给药的不可逆的H2-受体拮抗剂洛昔替丁0，8，和16周，ECL细胞转化监测通过评估胃泌素水平，粘膜组胺含量，和嗜铬粒蛋白免疫反应。纯化ECL细胞，并通过溴脱氧尿苷摄取来测量响应于胃泌素和TGF α的每个阶段的细胞增殖。TGF-α的表达通过放射免疫分析和北方印迹进行评估，表皮生长因子（EGF）受体的表达通过Western印迹，免疫沉淀和免疫细胞化学进行测定。尽管在高胃泌素血症期间对胃泌素的反应降低，但TGF-α对ECL细胞的增殖作用在增生的发展过程中被特异性放大。结论在低酸诱导的高胃泌素血症过程中，TGF-α和EGF受体的表达可能构成ECL细胞肿瘤转化的自分泌调节机制。（胃肠病学1996年11月;111（5）：1212-23）
BACKGROUND & AIMSGastric carcinoids evolved from enterochromaffin- like (ECL) cell hyperplasia are usually associated with high pH and hypergastrinemia. The Mastomys species exhibits a genetic propensity to gastric carcinoid formation that can be accelerated by acid inhibition- induced hypergastrinemia. Although gastrin is critical in the initiation of the ECL cell transformation, the role of other growth factors involved in the evolution of the tumor autonomy has not been established. The aim of this study was to evaluate the role of transforming growth factor (TGF) alpha in the regulation of ECL cell transformation.METHODSMastomys were orally administered an irreversible H2-receptor antagonist loxtidine for 0, 8, and 16 weeks, and ECL cell transformation was monitored by assessing gastrin levels, mucosal histamine content, and chromogranin immunoreactivity. The ECL cells were purified, and cell proliferation at each stage in response to gastrin and TGF alpha was measured by bromodeoxyuridine uptake. TGF- alpha expression was evaluated by radioimmunoassay and Northern blot, and epidermal growth factor (EGF) receptor expression was determined by Western blot, immunoprecipitation, and immunocytochemistry.RESULTSAlthough the response to gastrin decreased during hypergastrinemia, the proliferative effect of TGF-alpha on ECL cells was specifically amplified during the development of hyperplasia. TGF-alpha and EGF receptor expression increased steadily in the transformed cells.CONCLUSIONSDuring low acid-induced hypergastrinemia, the expression of TGF-alpha and EGF receptor may constitute an autocrine regulatory mechanism in ECL cell tumor transformation. (Gastroenterology 1996 Nov;111(5):1212-23)