Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor.
Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor.
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雌激素受体阳性乳腺癌具有患者特异性激素敏感性并依赖于孕酮受体。
DOI：
10.1038/s41467-022-30898-0
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发表时间：
2022-06-06
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
雌激素和孕激素受体（ER，PR）信号通路控制乳腺发育，并影响乳腺癌的发生。ER是ER +疾病的既定驱动因素，但PR本身是ER靶基因，其作用存在争议。我们通过遗传学方法在临床相关环境中评估该问题，并将ER +乳腺癌细胞系和患者来源的肿瘤细胞注射到免疫功能低下小鼠的乳管中。将这种ER +异种移植物暴露于生理相关水平的17-β-雌二醇（E2）和孕酮（P4）。我们发现绝经前E2和P4水平独立增加肿瘤生长，联合治疗增强转移扩散。增殖反应具有患者特异性，MYC和雄激素受体（AR）特征决定P4反应。PR是患者样品中肿瘤生长所需的，并且足以驱动ER信号传导消融的肿瘤细胞中的肿瘤生长和转移。我们的研究结果表明，内分泌治疗可能需要个性化，废除PR表达可能是一种治疗选择。孕激素受体（PR）及其与雌激素受体（ER）的相互作用在乳腺癌中的作用是有争议的。在这里，作者证明PR在乳腺癌生长和转移中具有ER非依赖性作用，其作用依赖于MYC和雄激素受体特征。
Estrogen and progesterone receptor (ER, PR) signaling control breast development and impinge on breast carcinogenesis. ER is an established driver of ER + disease but the role of the PR, itself an ER target gene, is debated. We assess the issue in clinically relevant settings by a genetic approach and inject ER + breast cancer cell lines and patient-derived tumor cells to the milk ducts of immunocompromised mice. Such ER + xenografts were exposed to physiologically relevant levels of 17-β-estradiol (E2) and progesterone (P4). We find that independently both premenopausal E2 and P4 levels increase tumor growth and combined treatment enhances metastatic spread. The proliferative responses are patient-specific with MYC and androgen receptor (AR) signatures determining P4 response. PR is required for tumor growth in patient samples and sufficient to drive tumor growth and metastasis in ER signaling ablated tumor cells. Our findings suggest that endocrine therapy may need to be personalized, and that abrogating PR expression can be a therapeutic option. The role of progesterone receptor (PR) and its interplay with estrogen receptor (ER) in breast cancer is controversial. Here, the authors demonstrate that PR can have an ER-independent role in breast cancer growth and metastasis and that its effects are dependent on MYC and androgen receptor signatures.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
3.5
作者：
Horwitz KB;Sartorius CA
通讯作者：
Sartorius CA
DOI：
10.1186/bcr1734
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Duss S;André S;Nicoulaz AL;Fiche M;Bonnefoi H;Brisken C;Iggo RD
通讯作者：
Iggo RD
影响因子：
8.8
作者：
Dwyer AR;Truong TH;Kerkvliet CP;Paul KV;Kabos P;Sartorius CA;Lange CA
通讯作者：
Lange CA
DOI：
10.1186/bcr2358
发表时间：
2009
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Behbod F;Kittrell FS;LaMarca H;Edwards D;Kerbawy S;Heestand JC;Young E;Mukhopadhyay P;Yeh HW;Allred DC;Hu M;Polyak K;Rosen JM;Medina D
通讯作者：
Medina D