Vitamin D3 receptor (VDR) expression in HC-11 mammary cells:: regulation by growth-modulatory agents, differentiation, and Ha-ras transformation

被引:32
作者
Escaleira, MTF [1 ]
Brentani, MM [1 ]
机构
[1] Univ Sao Paulo, Fac Med, Dept Radiol, Disciplina Oncol, BR-01246903 Sao Paulo, Brazil
基金
巴西圣保罗研究基金会;
关键词
cell proliferation; Ha-ras transformation; HC-11 mammary cells; mammary differentiation; VDR mRNA modulation; vitamin D-3;
D O I
10.1023/A:1006198107805
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
HC-11 mammary epithelial cells which originate from midpregnant BALB/c mice are able to differentiate in culture after epidermal (EGF) or basic fibroblast (FGF) growth factor pretreatment followed by lactogenic hormone stimulation (Dexamethasone, Insulin, and Prolactin - DIP). In our study, HC-11 cells exhibited specific vitamin D-3 receptors (VDR) determined by Northern analysis or flow cytometry and responded to 10 nM vitamin D-3 treatment displaying strong growth inhibition, arrest in G0/G1 phase without evidence of apoptosis, and VDR mRNA reduction, although the percentage of cells expressing VDR protein remained unchanged. In an attempt to verify if there was a correlation between the growth state of the cells and VDR levels, we have examined the effects of growth modulators such as EGF/bFGF and confluency and transformation by Ha-ras. A down-regulation of VDR expression was observed after Ha-ras transformation of HC-11 cells which desensitized the cells to the growth inhibitory effects of vitamin D-3. EGF or bFGF decreased VDR in parental cells and EGF antagonized the antiproliferative activity of vitamin D-3. As well, transition from proliferating to confluent state significantly reduced VDR levels only in parental cells. DIP-induced HC-11 cell differentiation (monitored by beta-casein transcripts), although leading to cell cycle arrest, increased VDR mRNA content, which seems to be rather related to lactogenic hormone induction than to differentiation itself. In fact, DIP-stimulated HC-11 cells in the absence of EGF pretreatment, or DIP-treated HC-11ras cultures, also displayed up-regulated VDR level even in the absence of differentiation. Concluding, mammary VDR levels might be regulated by growth modulating agents, by physiological conditions of the gland, and by the ras-mediated malignant transformation.
引用
收藏
页码:123 / 133
页数:11
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