Department of Oncology, Georgetown University, 3970 Reservoir Rd NW, Washington, DC, 20057, USA.
Department of Medicine, Georgetown University, Washington, DC, 20057, USA.
Sci Rep. 2022 Apr 22;12(1):6159. doi: 10.1038/s41598-022-10246-4.
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.
利用条件重编程细胞技术，从同侧乳腺癌浸润性乳腺癌的乳房切除术组织中进行原发性分离，研究了发生乳腺癌风险的非癌性人类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。相对活力和乳腺球体形成在样本之间存在差异，但在三种不同的乳腺特异性培养基中保持稳定。E2F 细胞周期靶基因表达水平与活力呈正相关，而年龄增长则呈负相关。雌激素生长反应与组织坏死因子信号和干扰素 α 反应基因富集相关。新辅助化疗暴露显著改变了转录组，使它们向与乳腺干细胞形成相关的基因表达转移。乳腺癌预后特征集包括在正常发育过程中仅限于妊娠或月经周期特定阶段的基因。对样本转录组进行了特定阶段基因表达模式的查询。所有癌症样本和一部分高危样本显示出重叠的阶段，反映了异常的基因表达模式，而其他高危样本则表现出更多的阶段特异性模式。总之，高危细胞保留了可能反映不同风险特征的行为和转录组多样性。有可能为高危乳腺细胞开发类似于用于乳腺癌的预后平台。
