Altered subcellular localization of p53 in estrogen-dependent and estrogen-independent breast cancer cells
Altered subcellular localization of p53 in estrogen-dependent and estrogen-independent breast cancer cells
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DOI：
10.1081/cnv-120002151
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发表时间：
2002-01-01
影响因子：
2.4
通讯作者：
Sidi, Y
中科院分区：
文献类型：
--
作者：
Lilling, G;Nordenberg, J;Sidi, Y
LCC2, all estradiol-independent tamoxifen (Tax)-resistant subline of MCF-7 human breast cancer cell line, is resistant relatively towards Tax and methotrexate (Mtx). The purpose of the present study is to evaluate the role of p53 ill determining this resistance. While MCF-7 is sensitive to and undergoes apoptosis, as determined by propidium iodide stain, by Tax and Mtx, LCC2 is resistant to apoptosis induction by these agents. Both cell lines undergo apoptosis and are sensitive equally to doxorubicin (Adr). p53 cDNA of both sublines was evaluated by polymerase chain reaction (PCR) amplification and sequencing and was found to be of wild-type. p53 mRNA, as well as protein, are elevated markedly ill LCC2 as compared to MCF-7 cells. p53 expression it-as increased by estradiol and Adr, not changed by Mtx, and decreased by Tax and estradiol-deprivation ill both sublines. p53 modulation by the various agents, ill both sublines, was evaluated by cytochemical staining and subcellular-fractionation. This analysis showed that p53 is localized mainly ill the nuclear fraction ill MCF-7 cells, and ill the cytoplasmatic fraction ill LCC2 cells. Doxorubicin induced apoptosis in MCF-7 cells along with increase ill its nuclear fraction. Ill contrast, LCC2 underwent apoptosis by Adr despite its cytoplasmatic sequestration. These experiments demonstrate that p53 is sequestered to cytoplasm in the estrogen-independent, Tax-resistant LCC2 cells. However, the differences in apoptotic rate between MCF-7 and LCC2 cells do not seem to be dependent on p53. The LCC2 cell line may serve as a useful model for the study of the mechanism of cytoplasmatic sequestration of wild type (wt) p53, its physiologic consequences, and its relation to estrogen-independence or Tax resistance of breast cancer cells.
