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首页> 外文期刊>Molecular and Cellular Biology >Wild-type p53 induces diverse effects in 32D cells expressing different oncogenes.
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Wild-type p53 induces diverse effects in 32D cells expressing different oncogenes.

机译：野生型p53在表达不同癌基因的32D细胞中诱导多种作用。

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Expression of exogenous wild-type (wt) p53 in different leukemia cell lines can induce growth arrest, apoptotic cell death, or cell differentiation. The hematopoietic cell lines that have been used so far to study wt p53 functions have in common the characteristic of not expressing endogenous p53. However, the mechanisms involved in the transformation of these cells are different, and the cells are at different stages of tumor progression. It can be postulated that each type of neoplastic cell offers a particular environment in which p53 might generate different effects. To test this hypothesis, we introduced individual oncogenes into untransformed, interleukin-3 (IL-3)-dependent myeloid precursor 32D cells to have a single transforming agent at a time. The effects induced by wt p53 overexpression were subsequently evaluated in each oncogene-expressing 32D derivative. We found that in not fully transformed, v-ras-expressing 32D cells, as already shown for the parental 32D cells, overexpression of the wt p53 gene caused no phenotypic changes and no reduction of the proliferative rate as long as the cells were maintained in their normal culture conditions (presence of IL-3 and serum). An accelerated rate of apoptosis was observed after IL-3 withdrawal. In contrast, in transformed, IL-3-independent 32D cells, wt p53 overexpression induced different effects. The v-abl-transformed cells manifested a reduction in growth rate, while the v-src-transformed cells underwent monocytic differentiation. These results show that the phenotype effects of wt p53 action(s) can vary as a function of the cellular environment.
机译：外源野生型（wt）p53在不同的白血病细胞系中的表达可诱导生长停滞，凋亡性细胞死亡或细胞分化。迄今已用于研究wt p53功能的造血细胞系的共同特征是不表达内源性p53。然而，这些细胞转化所涉及的机制是不同的，并且细胞处于肿瘤进展的不同阶段。可以推测，每种类型的肿瘤细胞都提供了一个特定的环境，其中p53可能会产生不同的作用。为了验证该假设，我们将单个癌基因引入未转化的白介素3（IL-3）依赖的髓样前体32D细胞中，一次仅具有一种转化剂。随后在每种表达癌基因的32D衍生物中评估了wt p53过表达诱导的效应。我们发现，在未完全转化，表达v-ras的32D细胞中（如对亲本32D细胞已显示的那样），wt p53基因的过表达不会引起表型变化，并且只要将细胞保持在原始状态就不会降低增殖率。它们的正常培养条件（存在IL-3和血清）。 IL-3撤离后观察到凋亡的加速速率。相反，在转化的，不依赖IL-3的32D细胞中，wt p53过表达诱导了不同的作用。 v-abl转化的细胞表现出生长速率的降低，而v-src转化的细胞经历了单核细胞分化。这些结果表明，wt p53作用的表型效应可随细胞环境而变化。

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