Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer.
Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer.
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DOI：
10.1038/s41416-022-01849-9
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发表时间：
2022-09
影响因子：
8.8
通讯作者：
Speers, Corey W.
中科院分区：
文献类型：
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作者：
Michmerhuizen, Anna R.;Lerner, Lynn M.;Ward, Connor;Pesch, Andrea M.;Zhang, Amanda;Schwartz, Rachel;Wilder-Romans, Kari;Eisner, Joel R.;Rae, James M.;Pierce, Lori J.;Speers, Corey W.
放射治疗（RT）和激素受体（HR）抑制用于治疗HR阳性乳腺癌；然而，对于雄激素受体（AR）和雌激素受体（ER）在AR阳性和ER阳性（AR+/ER+）乳腺癌中对RT的反应中相互作用知之甚少。在这里，我们使用AR和/或ER的药理学或遗传抑制/降解来评估AR+/ER+细胞系的放射致敏性。用AR拮抗剂（恩杂鲁胺、阿帕鲁胺、达鲁胺、七韦特奈尔、ARD-61）、内质网拮抗剂（他莫昔芬、氟维司汀）或去除AR来评估放射线致敏性。AR拮抗剂或内质网拮抗剂联合RT治疗不会导致放射线致敏改变（辐射增强比[rER]: 0.76-1.21）。氟维司汀治疗对CAMA-1和BT-474细胞（rER: 1.06-2.0）有显著的放射增敏作用，但对ZR-75-1细胞（rER: 0.9-1.11）没有显著的增敏作用。他莫昔芬联合恩杂鲁胺在1小时或1周的预处理中没有改变放射敏感性（rER: 0.95-1.14）。与Cas9细胞相比，AR基因敲除的放射敏感性没有变化（rER: 1.07±0.11），与Cas9细胞相比，他莫昔芬或氟维司汀没有实现额外的放射增敏（rER: 0.84-1.19）。虽然AR+ TNBC的放射增敏，但AR抑制并不调节AR+/ER+乳腺癌的放射敏感性。内质网拮抗剂联合RT的疗效也可能依赖于AR表达。
Radiation therapy (RT) and hormone receptor (HR) inhibition are used for the treatment of HR-positive breast cancers; however, little is known about the interaction of the androgen receptor (AR) and estrogen receptor (ER) in response to RT in AR-positive, ER-positive (AR+/ER+) breast cancers. Here we assessed radiosensitisation of AR+/ER+ cell lines using pharmacologic or genetic inhibition/degradation of AR and/or ER. Radiosensitisation was assessed with AR antagonists (enzalutamide, apalutamide, darolutamide, seviteronel, ARD-61), ER antagonists (tamoxifen, fulvestrant) or using knockout of AR. Treatment with AR antagonists or ER antagonists in combination with RT did not result in radiosensitisation changes (radiation enhancement ratios [rER]: 0.76–1.21). Fulvestrant treatment provided significant radiosensitisation of CAMA-1 and BT-474 cells (rER: 1.06–2.0) but not ZR-75-1 cells (rER: 0.9–1.11). Combining tamoxifen with enzalutamide did not alter radiosensitivity using a 1 h or 1-week pretreatment (rER: 0.95–1.14). Radiosensitivity was unchanged in AR knockout compared to Cas9 cells (rER: 1.07 ± 0.11), and no additional radiosensitisation was achieved with tamoxifen or fulvestrant compared to Cas9 cells (rER: 0.84–1.19). While radiosensitising in AR + TNBC, AR inhibition does not modulate radiation sensitivity in AR+/ER+ breast cancer. The efficacy of ER antagonists in combination with RT may also be dependent on AR expression.
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DOI：
10.1186/bcr969
发表时间：
2005
期刊：
Breast cancer research : BCR
影响因子：
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作者：
Azria D;Larbouret C;Cunat S;Ozsahin M;Gourgou S;Martineau P;Evans DB;Romieu G;Pujol P;Pèlegrin A
通讯作者：
Pèlegrin A
影响因子：
3.7
作者：
Holler M;Grottke A;Mueck K;Manes J;Jücker M;Rodemann HP;Toulany M
通讯作者：
Toulany M
影响因子：
4.8
作者：
Knudsen, KE;Arden, KC;Cavenee, KK
通讯作者：
Cavenee, KK
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Ward, Elizabeth
通讯作者：
Ward, Elizabeth
HER2 通过激活体外和体内粘着斑激酶降低乳腺癌放射敏感性
影响因子：
--
作者：
Hou J;Zhou Z;Chen X;Zhao R;Yang Z;Wei N;Ni Q;Feng Y;Yu X;Ma J;Guo X
通讯作者：
Guo X