Characterization of transcriptome diversity and in vitro behavior of primary human high-risk breast cells.

Characterization of transcriptome diversity and in vitro behavior of primary human high-risk breast cells.
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DOI:
10.1038/s41598-022-10246-4
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发表时间:
2022-04-22
期刊:
影响因子:
4.6
通讯作者:
Furth, Priscilla A.
Furth, Priscilla A.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Alothman, Sahar J.;Kang, Keunsoo;Liu, Xuefeng;Krawczyk, Ewa;Azhar, Redha, I;Hu, Rong;Goerlitz, David;Kallakury, Bhaskar, V;Furth, Priscilla A.

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在利用条件重编程细胞技术从乳腺切除术组织同侧至浸润性乳腺癌的初级分离后,探索了具有乳腺癌发展风险的非癌性人乳腺上皮细胞的生物学和转录组。培养物表现出一致的可分类行为。样品之间的相对活力和乳腺球形成不同,但在三种不同的乳腺特异性培养基中保持稳定。E2F细胞周期靶基因的表达水平与细胞活力呈正相关,年龄增长呈负相关。雌激素生长反应与组织坏死因子信号传导和干扰素α反应基因富集相关。新辅助化疗暴露显著改变了转录组,使其转向与乳腺干细胞形成相关的基因表达。乳腺癌预后标志集包括在正常发育中仅限于怀孕或月经周期的特定阶段的基因。查询样品转录组的阶段特异性基因表达模式。所有癌症样本和一部分高风险样本显示出反映异常基因表达模式的重叠阶段,而其他高风险样本则表现出更多阶段特异性模式。总之,处于风险中的细胞保留了行为和转录组的多样性,这些多样性可以反映不同的风险特征。有可能为高风险乳腺细胞开发类似于用于乳腺癌的预后平台。
Biology and transcriptomes of non-cancerous human mammary epithelial cells at risk for breast cancer development were explored following primary isolation utilizing conditional reprogramming cell technology from mastectomy tissue ipsilateral to invasive breast cancer. Cultures demonstrated consistent categorizable behaviors. Relative viability and mammosphere formation differed between samples but were stable across three different mammary-specific media. E2F cell cycle target genes expression levels were positively correlated with viability and advancing age was inversely associated. Estrogen growth response was associated with Tissue necrosis factor signaling and Interferon alpha response gene enrichment. Neoadjuvant chemotherapy exposure significantly altered transcriptomes, shifting them towards expression of genes linked to mammary stem cell formation. Breast cancer prognostic signature sets include genes that in normal development are limited to specific stages of pregnancy or the menstrual cycle. Sample transcriptomes were queried for stage specific gene expression patterns. All cancer samples and a portion of high-risk samples showed overlapping stages reflective of abnormal gene expression patterns, while other high-risk samples exhibited more stage specific patterns. In conclusion, at-risk cells preserve behavioral and transcriptome diversity that could reflect different risk profiles. It is possible that prognostic platforms analogous to those used for breast cancer could be developed for high-risk mammary cells.
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