Epithelial oestrogen receptor α is dispensable for the development of oestrogen-induced cervical neoplastic diseases.
Epithelial oestrogen receptor α is dispensable for the development of oestrogen-induced cervical neoplastic diseases.
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DOI：
10.1002/path.5069
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Chung SH
中科院分区：
文献类型：
--
作者：
Son J;Park Y;Chung SH
人乳头瘤病毒（HPV）是必需的，但不足以治疗宫颈癌（CxCa）。雌二醇（E2）在角蛋白14 （K14）启动子控制下，促进表达HPV16 E7癌蛋白的K14E7转基因小鼠中CxCa的发育。E2主要通过雌激素受体α (ERα)起作用。然而，ERα在人CxCa中的作用一直被低估，很大程度上是因为它不在癌细胞中表达。我们发现，K14E7小鼠宫颈间质中er1 （er α-编码基因）的缺失可促进宫颈上皮内瘤变（CIN）的消退，CIN是CxCa的前体病变。在这里，我们在宫颈上皮中删除了Esr1，但没有删除间质。我们发现E2可诱导上皮er α-缺陷小鼠的宫颈上皮细胞增殖。我们还发现E2促进了上皮细胞ERα-缺失的K14E7小鼠中CIN和CxCa的发展，所有肿瘤上皮细胞ERα均为阴性。此外，ERα−和ERα+ CxCa之间的增殖指标相似。这些结果表明上皮ERα对于e2诱导的CIN和CxCa不是必需的。综上所述，我们得出结论，基质ERα，而不是上皮ERα，在CxCa中介导致癌E2信号。我们的结果支持间质ERα信号作为疾病的治疗靶点。
Human papillomavirus (HPV) is required but not sufficient for cervical carcinoma (CxCa). Estradiol (E2) promotes CxCa development in K14E7 transgenic mice expressing the HPV16 E7 oncoprotein under the control of the keratin 14 (K14) promoter. E2 mainly works through estrogen receptor α (ERα). However, the role of ERα in human CxCa has been underappreciated largely because it is not expressed in carcinoma cells. We have shown that deletion of Esr1 (the ERα-coding gene) in the cervical stroma of K14E7 mice promotes regression of cervical intraepithelial neoplasia (CIN), the precursor lesion of CxCa. Here, we deleted Esr1 in the cervical epithelium but not stroma. We found that E2 induced cervical epithelial cell proliferation in epithelial ERα-deficient mice. We also found that E2 promoted the development of CIN and CxCa in epithelial ERα-deficient K14E7 mice, and all neoplastic epithelial cells were negative for ERα. In addition, proliferation indices were similar between ERα− and ERα+ CxCa. These results indicate that epithelial ERα is not necessary for E2-induced CIN and CxCa. Taken together, we conclude that stromal ERα, rather than epithelial ERα, mediates oncogenic E2 signaling in CxCa. Our results support stromal ERα signaling as a therapeutic target for the disease.
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影响因子：
--
作者：
Cunha, GR;Cooke, PS;Kurita, T
通讯作者：
Kurita, T
影响因子：
4.8
作者：
Daikoku, Takiko;Ogawa, Yuya;Dey, Sudhansu K.
通讯作者：
Dey, Sudhansu K.
DOI：
10.1073/pnas.1013226107
发表时间：
2010-11-09
影响因子：
11.1
作者：
Winuthayanon, Wipawee;Hewitt, Sylvia C.;Korach, Kenneth S.
通讯作者：
Korach, Kenneth S.
影响因子：
64.8
作者：
Cancer Genome Atlas Research Network;Albert Einstein College of Medicine;Analytical Biological Services;Barretos Cancer Hospital;Baylor College of Medicine;Beckman Research Institute of City of Hope;Buck Institute for Research on Aging;Canada's Michael Smith Genome Sciences Centre;Harvard Medical School;Helen F. Graham Cancer Center &Research Institute at Christiana Care Health Services;HudsonAlpha Institute for Biotechnology;ILSbio, LLC;Indiana University School of Medicine;Institute of Human Virology;Institute for Systems Biology;International Genomics Consortium;Leidos Biomedical;Massachusetts General Hospital;McDonnell Genome Institute at Washington University;Medical College of Wisconsin;Medical University of South Carolina;Memorial Sloan Kettering Cancer Center;Montefiore Medical Center;NantOmics;National Cancer Institute;National Hospital, Abuja, Nigeria;National Human Genome Research Institute;National Institute of Environmental Health Sciences;National Institute on Deafness &Other Communication Disorders;Ontario Tumour Bank, London Health Sciences Centre;Ontario Tumour Bank, Ontario Institute for Cancer Research;Ontario Tumour Bank, The Ottawa Hospital;Oregon Health &Science University;Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center;SRA International;St Joseph's Candler Health System;Eli &Edythe L. Broad Institute of Massachusetts Institute of Technology &Harvard University;Research Institute at Nationwide Children's Hospital;Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University;University of Bergen;University of Texas MD Anderson Cancer Center;University of Abuja Teaching Hospital;University of Alabama at Birmingham;University of California, Irvine;University of California Santa Cruz;University of Kansas Medical Center;University of Lausanne;University of New Mexico Health Sciences Center;University of North Carolina at Chapel Hill;University of Oklahoma Health Sciences Center;University of Pittsburgh;University of São Paulo, Ribeir ão Preto Medical School;University of Southern California;University of Washington;University of Wisconsin School of Medicine &Public Health;Van Andel Research Institute;Washington University in St Louis
通讯作者：
Washington University in St Louis
影响因子：
2.3
作者：
Hatch, EE;Herbst, AL;Robboy, SJ
通讯作者：
Robboy, SJ