Rapid induction of IgM-secreting murine plasmacytomas by pristane and an immunoglobulin heavy-chain promoter/enhancer-driven c-myc/v-Ha-ras retrovirus.

Rapid induction of IgM-secreting murine plasmacytomas by pristane and an immunoglobulin heavy-chain promoter/enhancer-driven c-myc/v-Ha-ras retrovirus.
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通过降植烷和免疫球蛋白重链启动子/增强子驱动的 c-myc/v-Ha-ras 逆转录病毒快速诱导分泌 IgM 的小鼠浆细胞瘤。

DOI:
10.1073/pnas.85.16.6067
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发表时间:
1988
影响因子:
11.1
通讯作者:
Marcu,KB
Marcu,KB
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Clynes,R;Wax,J;Stanton,LW;Smith-Gill,S;Potter,M;Marcu,KB

文献摘要

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一种逆转录病毒载体,RIM,含有免疫球蛋白重链基因启动子和增强子元件控制下的鼠c-myc和由莫洛尼鼠白血病病毒长末端重复序列驱动的v-Ha-ras,在28%的成年和83%的3周龄降植烷条件小鼠中诱导分泌IgM的浆细胞瘤,平均潜伏期为60-70天。相反,仅携带c-myc或v-Ha-ras的相同载体实际上是无效的。RIM诱导的浆细胞瘤表达逆转录病毒myc和ras基因,而其内源性c-myc等位基因未重排和转录活性。这些浆细胞瘤是克隆性的,因为每个浆细胞瘤都具有独特的免疫球蛋白重链连接区重排和单个重组前病毒。莫洛尼鼠白血病辅助病毒在肿瘤发生中没有发挥强制性作用,因为莫洛尼鼠白血病前病毒的插入仅在成年小鼠诱导的24个浆细胞瘤中的6个中发现。总而言之,这些发现支持了这样的观点:v-Ha-ras癌基因可以在姥鲛烷浆细胞发生中与激活的myc基因合作。
A retroviral vector, RIM, containing murine c-myc under the control of immunoglobulin heavy-chain gene promoter and enhancer elements and v-Ha-ras driven by a Moloney murine leukemia virus long terminal repeat induced IgM-secreting plasmacytomas in 28% of adult and 83% of 3-week-old pristane-conditioned mice with mean latency periods of 60-70 days. In contrast, the same vector only harboring c-myc or v-Ha-ras was virtually ineffective. RIM-induced plasmacytomas expressed retroviral myc and ras genes while their endogenous c-myc alleles were unrearranged and transcriptionally inactive. These plasmacytomas were clonal as each possessed a unique immunoglobulin heavy-chain joining region rearrangement and a single recombinant provirus. Moloney murine leukemia helper virus did not play an obligatory role in tumorigenesis since insertions of Moloney murine leukemia proviruses were found in only 6 of 24 plasmacytomas induced in adult mice. Taken together, these findings support the view that the v-Ha-ras oncogene can cooperate with an activated myc gene in pristane plasmacytomagenesis.