Polyamines induce malignant transformation in cultured NIH 3T3 fibroblasts

被引:36
|
作者
Tabib, A [1 ]
Bachrach, U [1 ]
机构
[1] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Biol, IL-91120 Jerusalem, Israel
来源
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY | 1998年 / 30卷 / 01期
关键词
polyamines; fibroblasts; transformation; soft agar; dexamethasone;
D O I
10.1016/S1357-2725(97)00073-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous studies have demonstrated that polyamines accumulate in cancer cells and that overproduction of ornithine decarboxylase (ODC), which catalyzes polyamine synthesis, elicits the acquisition of the transformed phenotype. However, it was not clear whether the overexpression of ODC and the accumulation of polyamines are only innocent by-products of the transformation process. In this study. we demonstrate that polyamines as such, may play a crucial role in malignant transformation. The system used consisted of NIH 3T3 fibroblasts transfected with a construct (pATMras) in which Ha-ras was under the transcriptional control of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) promoter (MMTVras cells). Dexamethasone, which activates the promoter, triggered phenotypic transformation. This was accompanied by an increase in ODC activity and polyamine accumulation. Cells, thus transformed, grew in soft agar and formed typical foci. alpha-Difluoromethylornithine (DFMO), which blocks polyamine synthesis, inhibited the dexamethasone-enhanced transformation. This inhibition was reversed by polyamines. Polyamines caused transformation of MMTVras cells in the absence of dexamethasone. Under these conditions. cells became anchorage independent. This phenomenon is not explained by the leakiness of Ins, since normal, immortalized NIH 3T3 fibroblasts, also grew in soft agar in the presence of polyamines. Taken together, these observations suggest that polyamines may stimulate malignant transformation of immortalized cells, in cooperation with other factors, such as oncogenes or genetic defects. (C) 1998 Elsevier Science Ltd. All rights reserved.
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页码:135 / 146
页数:12
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