Forkhead-box A1 suppresses the progression of endometrial cancer via crosstalk with estrogen receptor α.
Forkhead-box A1 suppresses the progression of endometrial cancer via crosstalk with estrogen receptor α.
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Forkhead-box A1 通过与雌激素受体 α 相互作用抑制子宫内膜癌的进展。
DOI：
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
X. Wan
中科院分区：
文献类型：
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作者：
Jingyun Wang;W. Bao;Meiting Qiu;Yun Liao;Qi Che;Tingting Yang;Xiao;Haifeng Qiu;X. Wan
FOXA 1是FOX类转录因子之一，其调控功能的机制已被广泛研究。然而，关于FOXA 1在子宫内膜癌（EC）中的活性和表达模式知之甚少。在本研究中，我们研究了FOXA 1在多种人类EC细胞系和临床样本的免疫组化，qRT-PCR和Western blot分析的水平。雌激素受体（ER）α阳性的EC细胞株中FOXA 1表达明显增高（P=0.0048）。在子宫内膜组织中，FOXA 1在正常子宫内膜和高分化子宫内膜癌组织中均显著上调（P<0.001）。通过MTT法、平板集落形成法和Transwell法对FOXA 1进行功能分析。结果显示，FOXA 1的强制表达抑制EC细胞增殖，而FOXA 1的缺失促进细胞活力，并与肿瘤发生有关。裸鼠肿瘤异种移植试验也证实了FOXA 1表达的消除促进了细胞增殖。此外，我们发现FOXA 1的敲低降低了ERα的表达，并且FOXA 1在EC细胞系中与该受体相互作用。总之，这些实验表明FOXA 1是EC中的肿瘤抑制因子，并且可能与ERα相互作用。
Mechanisms governing the function of Forkhead-box A1 (FOXA1), a member of the FOX class of transcription factors, have been extensively studied. However, little is known about the activities and expression pattern of FOXA1 in endometrial cancer (EC). In the present study, we investigated the level of FOXA1 in multiple human EC cell lines and clinical samples by immunohistochemistry, qRT-PCR and Western blot analysis. FOXA1 overexpression was observed in estrogen receptor (ER)α-positive EC cell lines (P=0.0048). In endometrial tissues, FOXA1 was significantly upregulated in both normal endometrium and well-differentiated endometrial cancer tissues (P<0.001). Functional analyses of FOXA1 were evaluated by MTT, plate colony formation and Transwell assay. The results revealed that forced expression of FOXA1 inhibited EC cell proliferation, whereas FOXA1 depletion promoted cell viability and was associated with tumorigenesis. The nude mouse tumor xenograft assay also confirmed that ablation of FOXA1 expression promoted cell proliferation. Furthermore, we found that knockdown of FOXA1 decreased the expression of ERα, and FOXA1 interacted with this receptor in the EC cell lines. Collectively, these experiments suggest that FOXA1 is a tumor suppressor in EC and has a possible interaction with ERα.
影响因子：
11.2
作者：
Lin Lin-Lin;Charles T. Miller;Jorge I. Contreras;M. Prescott;S. Dagenais;R. Wu;J. Yee;M. Orringer;David E. Misek;S. Hanash;T. Glover;D. Beer
通讯作者：
Lin Lin-Lin;Charles T. Miller;Jorge I. Contreras;M. Prescott;S. Dagenais;R. Wu;J. Yee;M. Orringer;David E. Misek;S. Hanash;T. Glover;D. Beer
影响因子：
16
作者：
Cirillo, LA;Lin, FR;Zaret, KS
通讯作者：
Zaret, KS