Shounan Y, Miller M, Symonds G
School of Physiology and Pharmacology, University of New South Wales, Sydney, Australia.
Exp Hematol. 1995 Jun;23(6):492-9.
The oncogene v-erb-B has been shown to transform pre-B lymphocytes and early erythroid precursor cells and has been implicated in leukemogenesis. We have examined the effect of this oncogene on the growth of a murine myeloid interleukin-3 (IL-3)-dependent cell line, FDC-P1, FDC-P1 cells were infected with a recombinant murine retrovirus containing v-erb-B. As a result, clonal IL-3-independent cell lines (FI-v-erb-B) were generated with a high level of v-erb-B expression and an altered morphology compared to parental FDC-PI cells. The F1-v-erb-B cells were tumorigenic and did not express or secrete IL-3, suggesting the acquisition of IL-3 independence by a non-autocrine mechanism. In addition to the formation of myeloid colonies, FI-v-erb-B cells, when grown in semi-solid medium with exogenous IL-3, erythropoietin (Epo), or IL-3 plus Epo, could also form erythroid and mixed-erythroid colonies. By contrast, parental FDC-P1 cells formed only myeloid colonies under the same conditions. Our results indicate that v-erb-B abrogates growth factor dependence in these cells and may cause lineage modulation by acting to allow the induction of erythroid differentiation in FI-v-erb-B cells.
致癌基因v-erb-B已被证明可转化前B淋巴细胞和早期红系前体细胞,并与白血病发生有关。我们研究了该致癌基因对小鼠髓样白细胞介素3(IL-3)依赖性细胞系FDC-P1生长的影响,用含有v-erb-B的重组鼠逆转录病毒感染FDC-P1细胞。结果,产生了克隆性IL-3非依赖性细胞系(FI-v-erb-B),与亲代FDC-P1细胞相比,其v-erb-B表达水平较高且形态发生改变。F1-v-erb-B细胞具有致瘤性,不表达或分泌IL-3,提示通过非自分泌机制获得了IL-3非依赖性。除了形成髓样集落外,FI-v-erb-B细胞在含有外源性IL-3、促红细胞生成素(Epo)或IL-3加Epo的半固体培养基中生长时,也能形成红系集落和混合红系集落。相比之下,亲代FDC-P1细胞在相同条件下仅形成髓样集落。我们的结果表明,v-erb-B消除了这些细胞对生长因子的依赖性,并可能通过诱导FI-v-erb-B细胞红系分化而导致谱系调节。