Elevated expression of Ha-ras is an early event in two-stage skin carcinogenesis in SENCAR mice.
Elevated expression of Ha-ras is an early event in two-stage skin carcinogenesis in SENCAR mice.
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Ha-ras 表达升高是 SENCAR 小鼠两阶段皮肤癌发生的早期事件。
DOI：
10.1093/carcin/7.9.1599
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发表时间：
1986
期刊：
影响因子：
4.7
通讯作者：
Slaga,TJ
中科院分区：
文献类型：
--
作者：
Pelling,JC;Ernst,SM;Strawhecker,JM;Johnson,JA;Nairn,RS;Slaga,TJ
在senar小鼠皮肤两阶段癌变的起始和促进的不同阶段，研究了ha -致癌基因在senar小鼠表皮中的表达变化。用200 nmol强效起始剂苯并[a]芘7,8 -二醇9,10 -环氧化合物抗（BPDE-anti）（+）对映体治疗成年senar小鼠，然后用肿瘤启动子12 - 0-十四烷酰基酚-13-醋酸酯（TPA）重复治疗。其他小鼠用BPDE-anti的（−）对映体“假”启动，该对映体作为肿瘤启动剂是无活性的。在肿瘤发生的8个不同阶段，从肿瘤前表皮和肿瘤中分离聚腺苷化RNA，并使用Northern blot杂交分析ha - ras表达的变化。早在tpa促进的乳头状瘤发生后7周，就观察到Ha-rasRNA水平显著增强。在未处理的表皮或（+）或（−）对映体处理的表皮中，只有微量的Ha-rasRNA存在，然后用TPA处理2-12次（乳头状瘤前期）。肿瘤DNA的Southern blot杂交表明，Ha-rasoncogene的表达增加不是由于基因扩增。我们得出结论，ha - ras表达水平升高可能发生在小鼠体内表皮细胞肿瘤发展的早期阶段，并可能在肿瘤发生中发挥作用。
Alterations in the expression of the Ha-rasoncogene were investigated in SENCAR mice epidermis at various stages of initiation and promotion during two-stage skin carcinogenesis in SENCAR mice. Adult SENCAR mice were treated with 200 nmol of the (+) enantiomer of benzo[a]pyrene 7, 8-diol 9, 10-epoxide-anti(BPDE-anti), a potent initiating agent, followed by repetitive treatments with the tumor promoter 12–0-tetradecanoylphorbol-13-acetate (TPA). Other mice were ‘sham’-initiated with the (−) enantiomer of BPDE-anti, which is inactive as a tumor initiator. Polyadenylated RNA was isolated from pre-tumor epidermis and tumors at eight different stages of tumorigenesis and analyzed for changes in Ha-rasexpression using Northern blot hybridization. Significantly enhanced levels of Ha-rasRNA were observed in TPA-pro-moted papillomas as early as 7 weeks after initiation. Only trace amounts of Ha-rasRNA were present in untreated epidermis or epidermis treated with the (+) or (−) enantiomer followed by 2-12 treatments with TPA (pre-papilloma stage). Southern blot hybridization of tumor DNA indicated that the increased expression of the Ha-rasoncogene was not due to gene amplification. We conclude that elevated levels of Ha-rasexpression can occur at an early stage of tumor development in mouse epidermisin vivoand may play a role in tumorigenesis.