Direct tumorigenic conversion of human gallbladder carcinoma cells by v‐src but not by activated c‐H‐ras oncogene
Direct tumorigenic conversion of human gallbladder carcinoma cells by v‐src but not by activated c‐H‐ras oncogene
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通过 v-src 而不是通过激活的 c-H-ras 癌基因直接使人胆囊癌细胞发生致瘤
DOI：
10.1002/ijc.2910610211
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发表时间：
1995
影响因子：
6.4
通讯作者：
Y. Niho
中科院分区：
文献类型：
--
作者：
T. Tatsumoto;S. Nakano;K. Shimizu;M. Ono;T. Esaki;K. Ohshima;Y. Niho
通过将非致瘤性HAG-1人胆囊癌细胞与pSV 2 neo质粒和携带激活的c-H-ras或v-src癌基因的质粒共转染，研究了激活的ras和src癌基因产物在人胆囊腺癌细胞获得完全肿瘤表型中的作用。分离G-418抗性克隆，并评估其获得锚定非依赖性生长潜力。10个单独转染pSV 2neo的克隆和17个转染活化c-H-ras的克隆（包括4个表达突变p21 H-ras蛋白的克隆）均不能在软琼脂中形成集落。相比之下，在10个转染v-SRC的克隆中，有2个在软琼脂中形成集落并在无胸腺裸小鼠中产生肿瘤，产生的进行性肿瘤是低分化腺癌。这些致瘤性克隆显示具有p60 v-src蛋白的v-src DNA和mRNA水平，但在致瘤性转化后没有显著的染色体改变。此外，除莠霉素A（一种选择性src激酶抑制剂）显著降低了这些细胞在软琼脂中的克隆形成生长，而不是单层生长，表明v-src转化的HAG-1细胞的锚定非依赖性生长可能直接由p60 v-src激酶活性驱动。综上所述，我们的数据表明，HAG-1细胞的完全肿瘤转化取决于src相关的酪氨酸激酶活性，而不仅仅是活化的ras介导的功能，从而为人胆囊腺癌细胞获得致瘤潜力的src相关信号通路提供了证据。© 1995 Wiley利斯公司
The roles of activated ras and src oncogene products in the acquisition of fully neoplastic phenotype by human gallbladder adenocarcinoma cells were investigated by co‐transfecting non‐tumorigenic HAG‐1 human gallbladder carcinoma cells with the pSV2neo plasmid and a plasmid carrying either activated c‐H‐ras or v‐src oncogene. G‐418‐resistant clones were isolated and assessed for the acquisition of anchorage‐independent growth potential. Neither the 10 established clones transfected with pSV2neo alone nor the 17 clones transfected with activated c‐H‐ras, including 4 clones expressing the mutated p21H‐ras protein, could form colonies in soft agar. By contrast, out of 10 clones transfected with v‐src, 2 formed colonies in soft agar and produced tumors in athymic nude mice, the resulting progressive neoplasms being poorly differentiated adenocarcinomas. These tumorigenic clones were shown to have v‐src DNA and mRNA levels with p60v‐src protein, but there were no significant chromosomal alterations following tumorigenic conversion. Moreover, herbimycin A, a selective src‐kinase inhibitor, markedly reduced clonogenic growth of these cells in soft agar rather than monolayer growth, suggesting that anchorage‐independent growth of the v‐src‐transformed HAG‐1 cells might be driven directly by p60v‐src kinase activity. Taken together, our data suggest that the fully neoplastic conversion of HAG‐1 cells depends on src‐related tyrosine‐kinase activity, but not solely on the function mediated by activated ras, thus providing evidence of an src‐related signaling pathway for the acquisition of tumorigenic potential by human gallbladder adenocarcinoma cells. © 1995 Wiley‐Liss, Inc.
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影响因子：
11.2
作者：
Joyce Bos
通讯作者：
Joyce Bos
整合素信号传导：对肿瘤发生的影响。
影响因子：
11.2
作者：
Schwartz,MA
通讯作者：
Schwartz,MA
猿猴病毒 40 永生化人尿路上皮细胞的 EJ/ras 肿瘤转化：罕见事件。
影响因子：
11.2
作者：
Christian,BJ;Kao,CH;Wu,SQ;Meisner,LF;Reznikoff,CA
通讯作者：
Reznikoff,CA
H-ras 将 NIH/3T3 转化为锚定独立性，并伴有抑制活性的丧失。
影响因子：
3.7
作者：
Tolsma,SS;Cohen,JD;Ehrlich,LS;Bouck,NP
通讯作者：
Bouck,NP
影响因子：
15.9
作者：
CARTWRIGHT, CA;KAMPS, MP;ECKHART, W
通讯作者：
ECKHART, W