Effects of okadaic acid on calcitriol- and phorbol ester-induced expression and phosphorylation of osteopontin in mouse JB6 epidermal cells.
Effects of okadaic acid on calcitriol- and phorbol ester-induced expression and phosphorylation of osteopontin in mouse JB6 epidermal cells.
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冈田酸对骨化三醇和佛波酯诱导的小鼠 JB6 表皮细胞中骨桥蛋白表达和磷酸化的影响。
DOI：
10.1111/j.1749-6632.1995.tb44617.x
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发表时间：
1995
影响因子：
5.2
通讯作者：
Prince,CW
中科院分区：
文献类型：
--
作者：
Chang,PL;Yang,WC;Prince,CW
正常细胞转化为肿瘤细胞的过程通常可分为三个步骤：起始、促进和进展。Colburn及其同事开发的克隆小鼠表皮细胞JB6家族包括促进抗性（P-），促进敏感性（P+）或不可逆转化（TX）的克隆系。P+系是启动细胞，而不是转化细胞，因此为研究肿瘤发生促进阶段发生的分子事件提供了很好的模型。在这些细胞中，磷酯肿瘤启动子12-0-十四烷酰基磷酯-13-醋酸酯（TPA）诱导不可逆的致瘤转化。这种转化的细胞在裸鼠体内形成肿瘤，在软琼脂中生长时形成大的菌落。几年前，Smith和Denhardt发现，用TPA处理P+细胞系（JB6 C122）可以极大地诱导一种mRNA。通过Craig、Denhardt和其他人的工作，发现这种mRNA编码骨桥蛋白（OPN）。4 OPN的表达，以前被Senger称为转化依赖性分泌磷酸化蛋白5，现在已知与许多细胞类型的致瘤性转化有关。此外，最近的两项研究表明，OPN的表达不仅在肿瘤发生中起因果作用，而且在肿瘤转移中也起因果作用，这两项研究表明，OPN反义的表达可以部分或完全剥夺正常转移细胞在体内转移或形成肿瘤的能力。因此，促生过程中OPN的表达可能是肿瘤发生的必要步骤。我们在这里报道的工作旨在了解OPN的表达和磷酸化是如何在JB6肿瘤促进模型中被调节的。a本文报道的研究由NIH资助DE06739和DEW247给CWP。相应的作者。
The transformation of a normal cell into a tumor cell typically involves a process that can be summarized by three steps: initiation, promotion and progression. The JB6 family of clonal mouse epidermal cells developed by Colburn and co-workers includes clonal lines that are promotion-resistant (P-), promotion-sensitive (P+) or irreversibly transformed (TX).',~ The P+ lines are initiated but not transformed cells and thus provide good models for studying the molecular events that occur during the promotion phase of tumorigenesis. In these cells the phorbol ester tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA)-induces an irreversible tumorigenic transformation. Such transformed cells form tumors in nude mice and form large colonies when grown in soft agar. Several years ago Smith and Denhardt) discovered an mRNA that was greatly induced by treating one of the P+ cell lines (JB6 C122) with TPA. Through the work of Craig, Denhardt and others this mRNA was found to code for the phosphoprotein osteopontin (OPN). 4 Expression of OPN, formerly called transformation-dependent secreted phosphoprotein by Senger, 5 is now known to be linked to tumorigenic transformation of many cell types. Furthermore, a causal role for OPN expression in not only tumorigenesis but also metastasis is suggested by two recent studies which showed that expression of OPN antisense could partially or completely abrogate the ability of normally metastatic cells to metastasize or form tumors in~ ivo.~,'Thus, OPN expression during promotion could be a necessary step in tumorigenesis. Our work reported here is directed at understanding how OPN expression and phosphorylation is regulated in the JB6 model of tumor promotion. a The research reported here was supported by NIH grants DE06739 and DEW247 to CWP. Corresponding author.