Gastrin-regulated expression of p53 in transformed enterochromaffin-like cells in the African rodent mastomys.
Gastrin-regulated expression of p53 in transformed enterochromaffin-like cells in the African rodent mastomys.
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DOI：
10.1097/00004836-199800001-00019
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发表时间：
1998
影响因子：
2.9
通讯作者：
E. A. Luque;L. Tang;K. Borteçen;M. Kidd;K. Miu;J. Efstathiou;I. Modlin
中科院分区：
文献类型：
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作者：
E. A. Luque;L. Tang;K. Borteçen;M. Kidd;K. Miu;J. Efstathiou;I. Modlin
肿瘤抑制因子p53在细胞周期的G1/S期检查点起作用，以指导已经积累了体细胞突变的细胞走向凋亡并远离有丝分裂。p53基因通常在人类癌症中发生突变，但调控这一事件的分子机制尚不清楚。非洲啮齿类动物乳鼠表现出遗传易感性，发展胃类癌来源于肠嗜铬样（ECL）细胞。酸抑制诱导的高胃泌素血症可加速ECL细胞转化。本研究评价了p53在ECL细胞快速转化过程中的变化。高胃泌素血症产生的不可逆的组胺-2受体拮抗剂洛西丁8周（增生）和16周（肿瘤）。通过Western印迹分析和免疫组化使用抗野生型p53的单克隆抗体在不同转化阶段的胃底粘膜中评价p53表达。从纯化的ECL细胞中分离p53 mRNA，进行RT-PCR和分子序列分析。过度生产的野生型p53在高胃泌素血症的ECL细胞是显而易见的，和p53的分子特征，确定在幼稚和转化的ECL细胞。高胃泌素血症诱导的ECLoma中p53在C-末端发生突变。因此，在高胃泌素血症诱导的ECLoma的发展过程中，p53从过度产生变为突变，因此它可能在细胞转化中起作用。
The tumor suppressor p53 functions at the G1/S-phase checkpoint of the cell cycle to direct cells that have accumulated somatic mutations toward apoptosis and away from mitosis. The p53 gene is commonly mutated in human cancers, but the molecular mechanisms regulating this event are not clear. The African rodent mastomys exhibits a genetic predisposition to develop gastric carcinoids derived from enterochromaffin-like (ECL) cells. The ECL cell transformation can be accelerated by acid inhibition-induced hypergastrinemia. This study evaluates the alteration of p53 during the rapid ECL cell transformation. Hypergastrinemia was generated by the irreversible histamine-2 receptor antagonist loxtidine for 8 weeks (hyperplasia) and 16 weeks (neoplasia). p53 expression was evaluated in fundic mucosa from different stages of transformation by Western blot analysis and immunohistochemistry using monoclonal antibodies against wild-type p53. RT-PCR and molecular sequence analysis of p53 were undertaken with mRNA isolated from purified ECL cells. Overproduction of the wild type of p53 was evident in ECL cells during hypergastrinemia, and the molecular characteristics of p53 were determined in naive and transformed ECL cells. p53 was mutated at the C-terminus in ECLoma induced by hypergastrinemia. Therefore, p53 is altered from overproduction to mutation during the development of hypergastrinemia-induced ECLoma and it may therefore play a role in the cell transformation.