GROWTH-FACTORS IN PROGRESSION OF HUMAN ESOPHAGEAL AND GASTRIC CARCINOMAS
GROWTH-FACTORS IN PROGRESSION OF HUMAN ESOPHAGEAL AND GASTRIC CARCINOMAS
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DOI：
10.1016/s0232-1513(11)80316-6
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发表时间：
1990-01-01
期刊：
影响因子：
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通讯作者：
TAHARA, E
中科院分区：
文献类型：
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作者：
YOSHIDA, K;YASUI, W;TAHARA, E
人食道癌和胃癌表达多种自分泌生长因子和激素，包括表皮生长因子(EGF)、转化生长因子(TGF)α和β、血小板衍生生长因子(PDGF)、胰岛素样生长因子(IGF)和性激素。肿瘤细胞中EGF、转化生长因子-α及其受体(EGFR)的过度表达与肿瘤的侵袭和患者预后密切相关。EGF和TGF-α作为自分泌生长因子，诱导多种生长因子及其受体(EGF、TGF-α、EGFR、ERBB2、PDGF)的mRNAs表达，证实了这一点。此外，它们还能刺激金属蛋白酶基因的表达，提示EGF和转化生长因子-α相继引起级联现象，最有利于肿瘤的进展、侵袭和转移。另一方面，在肿瘤的发展过程中会发生多种癌基因的改变。HST-1和INT-2基因是成纤维细胞生长因子基因家族的成员之一，在约50%的食管癌原发灶和所有转移瘤中都有扩增。转移性胃癌中ERBB2基因扩增的频率高于原发癌。多种生长因子受体系统的过度表达可能导致基因改变。硬化性胃癌具有巨大的纤维间质，生长迅速且广泛，表现出高度的恶性度。其纤维间质可能是肿瘤细胞同步过度表达EGF、TGF-α、PDGF、IGF和TGF-β的原因之一。高分化腺癌多表现为p185ERBB2过度表达和p185ERBB2共表达，且EGFR与肿瘤的恶性程度密切相关。总之，肿瘤细胞产生的几种生长因子的积累和相互作用对于人类食道癌和胃癌的发展是必要的。这可能归因于基因的改变，包括癌基因的激活、抑癌基因和转录调控序列的失活和缺失。
Human esophageal and gastric carcinomas express multi-autocrine growth factors and hormones including epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and beta, platelet-derived growth factor (PDGF), insulin-like growth factor (IGF) and sex hormones. Overexpression of EGF, TGF-alpha and EGF receptor (EGFR) by tumor cells is closely correlated with the tumor invasion and patient prognosis. This is substantiated by the facts that EGF and TGF-alpha act as autocrine growth factors and then induce the expression of mRNAs for multi-growth factors and their receptors (EGF, TGF-alpha, EGFR, ERBB2, PDGF). Moreover, they stimulate the expression of metalloproteinase genes suggesting that EGF and TGF-alpha successively evoke cascade phenomena which are most convenient for tumor progression, invasion and metastasis. On the other hand, multiple oncogene alterations take place in the process of tumor progression. HST-1 and INT-2 genes which is a member of fibroblast growth factor gene family, are amplified in approximately 50 % of primary tumors and all the metastatic tumors of esophageal carcinomas. The amplification of ERBB2 gene in metastatic gastric carcinomas is detected more frequently than in primary carcinomas. Overexpression of multi-growth factor-receptor systems might lead to genetical alterations.Scirrhous gastric carcinoma has vast fibrous stroma with rapid and extensive growth and exhibits high malignancy. Its fibrous stroma may account for synchronous overexpression of EGF, TGF-alpha, PDGF, IGF and TGF-beta by tumor cells. Most of well differentiated adenocarcinomas show overexpression of p 185ERBB2 and coexpression of p 185ERBB2, and EGFR evidently correlates with high malignancy. In conclusion, the accumulation and interaction of several growth factors produced by tumor cells are necessary for the progression of human esophageal and gastric carcinomas. They may be attributed to genetic changes including activation of oncogenes, inactivation and deletion of anti-oncogenes and transcriptional regulatory sequences.