Pregnane X receptor suppresses proliferation and tumourigenicity of colon cancer cells.
Pregnane X receptor suppresses proliferation and tumourigenicity of colon cancer cells.
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DOI：
10.1038/sj.bjc.6605677
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发表时间：
2010-06-08
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
孕烷X受体（Pregnane X receptor，PXR）是一种核受体，调节各种外源性物质和内源性物质的代谢和处置。我们在这项研究中研究了PXR在调节结肠肿瘤发生中的新功能。组织化学、转染、细胞增殖测定、锚定-α依赖性测定、异种移植、免疫组织化学、免疫荧光流式细胞术。利用组织化学分析，我们发现PXR表达在许多结肠肿瘤中丢失或大大减少。通过细胞增殖试验和锚定非依赖性试验确定，通过将PXR稳定转染到结肠癌细胞系HT 29中的人PXR的异位表达显著抑制细胞增殖。孕烷X受体显著抑制HT 29裸鼠移植瘤的生长（310± 6.2mg vs 120±6 mg，P<0.01）。对切除的异种移植肿瘤组织进行Ki-67的免疫组织化学和免疫荧光分析表明，PXR抑制癌细胞增殖。PXR和Ki-67的表达是相互排斥的。流式细胞仪分析表明PXR可使细胞周期阻滞于G 0/G1期。PXR可显著上调p21 WAF 1/CIP 1的表达，而抑制E2 F1的表达。PXR通过调控p21 WAF 1/CIP 1和E2 F/Rb信号通路，将细胞周期控制在G 0/G1期，从而抑制结肠癌细胞的增殖和致瘤性。
Pregnane X receptor (PXR) is a nuclear receptor that regulates the metabolism and disposition of various xenobiotics and endobioitics. We investigated a novel PXR function in regulating colon tumourigenesis in this study. Histochemistry, transfection, cell proliferation assay, anchorage-α-dependent assay, xenograft, immunohistochemistry, immunofluorescence flow cytometry. Using histochemistry analysis, we found that PXR expressions were lost or greatly diminished in many colon tumours. Ectopic expression of human PXR through stable transfection of PXR into colon cancer cell line HT29 significantly inhibited cell proliferation as determined by cell proliferation assay and anchorage-independent assay. Pregnane X receptor suppressed significantly HT29 xenograft tumour growth in nude mice compared with control (310±6.2 vs 120±6 mg, P<0.01). Immunohistochemistry and immunofluorescence analysis of Ki-67 on excised xenograft tumour tissues showed that PXR inhibited cancer cell proliferation. Furthermore, expressions of PXR and Ki-67 were mutually exclusive. The flow cytometry analysis indicated that PXR caused G0/G1 cell-cycle arrest. p21WAF1/CIP1 expression was markedly elevated whereas E2F1 expression was inhibited by PXR. PXR inhibits the proliferation and tumourigenicity of colon cancer cells by controlling cell cycle at G0/G1 cell phase by regulating p21WAF1/CIP1 and E2F/Rb pathways.
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DOI：
10.1073/pnas.95.21.12208
发表时间：
1998-10-13
影响因子：
11.1
作者：
Bertilsson, G;Heidrich, J;Berkenstam, A
通讯作者：
Berkenstam, A
影响因子：
3.8
作者：
Naspinski, Christine;Gu, Xinsheng;Tian, Yanan
通讯作者：
Tian, Yanan
DOI：
10.1073/pnas.212494599
发表时间：
2002-10-15
影响因子：
11.1
作者：
Sonoda, J;Xie, W;Evans, RM
通讯作者：
Evans, RM
影响因子：
11.5
作者：
Gupta, Divya;Venkatesh, Madhukumar;Mani, Sridhar
通讯作者：
Mani, Sridhar
影响因子：
4.9
作者：
Martinez, Alfonso;Marquez, Ana;Urcelay, Elena
通讯作者：
Urcelay, Elena