HSF1 is a well-known heat shock protein expression regulator in response to stress. It also regulates processes important for growth, development or tumorigenesis. We studied the HSF1 influence on the phenotype of non-tumorigenic human mammary epithelial (MCF10A and MCF12A) and several triple-negative breast cancer cell lines. MCF10A and MCF12A differ in terms of HSF1 levels, morphology, growth in Matrigel, expression of epithelial (CDH1) and mesenchymal (VIM) markers (MCF10A are epithelial cells; MCF12A resemble mesenchymal cells). HSF1 down-regulation led to a reduced proliferation rate and spheroid formation in Matrigel by MCF10A cells. However, it did not affect MCF12A proliferation but led to CDH1 up-regulation and the formation of better organized spheroids. HSF1 overexpression in MCF10A resulted in reduced CDH1 and increased VIM expression and the acquisition of elongated fibroblast-like morphology. The above-mentioned results suggest that elevated levels of HSF1 may direct mammary epithelial cells toward a mesenchymal phenotype, while a lowering of HSF1 could reverse the mesenchymal phenotype to an epithelial one. Therefore, HSF1 may be involved in the remodeling of mammary gland architecture over the female lifetime. Moreover, HSF1 levels positively correlated with the invasive phenotype of triple-negative breast cancer cells, and their growth was inhibited by the HSF1 inhibitor DTHIB.
HSF1是众所周知的应激反应中热休克蛋白表达调控因子，同时也参与调控生长、发育及肿瘤发生等重要过程。本研究探讨了HSF1对非致瘤性人乳腺上皮细胞（MCF10A与MCF12A）及多种三阴性乳腺癌细胞表型的影响。MCF10A与MCF12A在HSF1表达水平、细胞形态、基质胶生长能力以及上皮标志物（CDH1）与间质标志物（VIM）表达方面存在差异（MCF10A呈上皮细胞特性，MCF12A则类似间质细胞）。下调HSF1可降低MCF10A细胞的增殖速率并抑制其在基质胶中的球体形成能力。然而，HSF1下调虽未影响MCF12A的增殖，却导致CDH1表达上调并形成结构更规整的球体。在MCF10A中过表达HSF1则引起CDH1表达下降、VIM表达升高，并使其获得细长成纤维细胞样形态。上述结果表明，HSF1水平升高可能促使乳腺上皮细胞向间质表型转化，而降低HSF1水平则可能逆转间质表型向上皮表型回归。因此，HSF1可能参与女性生命周期中乳腺结构的重塑过程。此外，在三阴性乳腺癌细胞中，HSF1水平与侵袭性表型呈正相关，其生长可被HSF1抑制剂DTHIB所抑制。
An Increase in HSF1 Expression Directs Human Mammary Epithelial Cells toward a Mesenchymal Phenotype
肿瘤(癌症)患者之家