Expression of the aryl hydrocarbon receptor is not required for the proliferation, migration, invasion, or estrogen-dependent tumorigenesis of MCF-7 breast cancer cells.
Expression of the aryl hydrocarbon receptor is not required for the proliferation, migration, invasion, or estrogen-dependent tumorigenesis of MCF-7 breast cancer cells.
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DOI：
10.1002/mc.21889
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发表时间：
2013-07
影响因子：
4.6
通讯作者：
Spink, David C.
中科院分区：
文献类型：
--
作者：
Spink, Barbara C.;Bennett, James A.;Lostritto, Nicole;Cole, Jacquelyn R.;Spink, David C.
AhR最初被鉴定为介导氯代二恶英和多环芳烃对细胞色素P450 1（CYP 1）表达影响的配体激活的转录因子。最近，有证据支持AhR参与细胞周期调控和肿瘤发生。为了进一步确定AhR在癌症中的作用，我们研究了AhR表达对MCF-7人乳腺癌细胞的细胞增殖、迁移、侵袭和肿瘤发生的影响。在这些研究中，将MCF-7细胞的性质与两种MCF-7衍生的亚系的性质进行了比较：表达最小AhR的AHR 100和过表达AhR的AhRexp。定量PCR、Western免疫印迹、17β-雌二醇（E2）代谢试验和乙氧基试卤灵O-脱乙基酶试验显示，AHR 100细胞中AhR表达缺失，AhR调节的CYP 1表达缺失，而AhRexp细胞中AhR和CYP 1表达增强。在1 nM E2的存在下，三种细胞系的细胞增殖速率与AhR mRNA水平呈负相关。与MCF-7和AhRexp细胞相比，AHR 100细胞在软琼脂中产生更多的集落，并且在以E2作为化学引诱物的小室测定中显示出增强的迁移和侵袭。尽管缺乏显着的AhR表达，AHR 100细胞保留了在严重的联合免疫缺陷小鼠中形成肿瘤的能力，当补充E2时，产生的平均肿瘤体积与MCF-7细胞观察到的相当。这些研究表明，虽然CYP 1表达和诱导高度依赖于AhR表达，但MCF-7细胞的增殖、侵袭、迁移、锚定非依赖性生长和雌激素刺激的肿瘤形成不需要AhR。
The AhR was initially identified as a ligand-activated transcription factor mediating effects of chlorinated dioxins and polycyclic aromatic hydrocarbons on cytochrome P450 1 (CYP1) expression. Recently, evidence supporting involvement of the AhR in cell-cycle regulation and tumorigenesis has been presented. To further define the roles of the AhR in cancer, we investigated the effects of AhR expression on cell proliferation, migration, invasion, and tumorigenesis of MCF-7 human breast cancer cells. In these studies, the properties of MCF-7 cells were compared with those of two MCF-7-derived sublines: AHR100, which express minimal AhR, and AhRexp, which overexpress AhR. Quantitative PCR, Western immunoblots, 17β-estradiol (E2) metabolism assays, and ethoxyresorufin O-deethylase assays showed the lack of AhR expression and AhR-regulated CYP1 expression in AHR100 cells, and enhanced AhR and CYP1 expression in AhRexp cells. In the presence of 1 nM E2, rates of cell proliferation of the three cell lines showed an inverse correlation with the levels of AhR mRNA. In comparison with MCF-7 and AhRexp cells, AHR100 cells produced more colonies in soft agar and showed enhanced migration and invasion in chamber assays with E2 as the chemoattractant. Despite the lack of significant AhR expression, AHR100 cells retained the ability to form tumors in severe combined immunodeficient mice when supplemented with E2, producing mean tumor volumes comparable to those observed with MCF-7 cells. These studies indicate that, while CYP1 expression and inducibility are highly dependent on AhR expression, the proliferation, invasion, migration, anchorage-independent growth, and estrogen-stimulated tumor formation of MCF-7 cells do not require the AhR.
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影响因子：
4.1
作者：
Chowdhury, Goutam;Dostalek, Miroslav;Hsu, Erin L.;Nguyen, Linh P.;Stec, Donald F.;Bradfield, Christopher A.;Guengerich, F. Peter
通讯作者：
Guengerich, F. Peter
DOI：
10.1073/pnas.0701764104
发表时间：
2007-05-22
影响因子：
11.1
作者：
Fritsche, Ellen;Schaefer, Claudia;Krutmann, Jean
通讯作者：
Krutmann, Jean
影响因子：
4.1
作者：
Nguyen, Linh P.;Hsu, Erin L.;Bradfield, Christopher A.
通讯作者：
Bradfield, Christopher A.
影响因子：
4.8
作者：
Ge, NL;Elferink, CJ
通讯作者：
Elferink, CJ
影响因子：
2.3
作者：
Casado, Fanny L.;Singh, Kameshwar P.;Gasiewicz, Thomas A.
通讯作者：
Gasiewicz, Thomas A.