A study on the biological function of heat shock factor 1 proteins in breast cancer

Abstract

The present study aimed to investigate the effect of HSF1 proteins on cell proliferation, apoptosis and invasion of breast cancer. The Michigan Cancer Foundation-7 (MCF-7) HSF1-knocked down stable cell line (experimental group) and control cell line (control group) were obtained using a lentivirus assay, and the effects of HSF1 knockdown on the proliferation, tumor formation, apoptosis and invasion ability were analyzed, respectively. The effects of HSF1 on downstream signals were analyzed using western blotting. Western blotting results showed that lentivirus successfully established a HSF1 knockdown stable cell line of MCF-7. Compared with the control group, the growth rate of MCF-7 cells in the experimental group was significantly decreased (P<0.05). Flow cytometry showed that the proportion of apoptosis in the control group was significantly lower than that of the experimental group (P<0.05). Notably, the invasion ability of cells in the control group was significantly higher than that in the experimental group (P<0.05). Compared with cells in the control group, the levels of heat shock protein (HSP)70, HSP90, anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and macrophage migration inhibitory factor (MIF) in the experimental group were significantly downregulated, whereas the level of Bax was significantly increased (P<0.05). In conclusion, HSF1 protein, as a transcription factor, regulates the expression levels of HSP70, HSP90, MIF, Bcl-2 and Bax, thus controlling the proliferation, apoptosis and invasion of cells. These findings suggest HSF1 protein as a potential target for the treatment of breast cancer.

Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy

“…In fact, the increased expression and activity of HSF1 are observed in a variety of cancers, such as prostate and breast cancers, in advanced stages, suggesting HSF1 as an important regulator of tumor progression and metastasis [79][80][81][82][83]. As the upstream modulator of various pathophysiological proteins such as HSP70, HSP90, MIF, Bcl2, and Bax, HSF1 assists in multiple parts of malignancy, including proliferation, migration, invasion, and inhibition of apoptosis [84,85]. Furthermore, HSF1 functions to allow cancer cell formation and progression by inducing genomic instability and stabilizing mitotic spindle organization through regulation of Cyclin D, p21, and p27 during mitosis [86][87][88].…”

Copper overload impairs hematopoietic stem and progenitor cell proliferation via prompting HSF1/SP1 aggregation and the subsequently downregulating FOXM1-Cytoskeleton axis

“…The mRNA levels of hsf1 and sp1 showed identical in runx1 GFP + cells and in runx1 GFP − cells, and maintained stable in runx1 GFP + cells after Cu stresses ( Figure S10 E). However, SP1, MYC-SP1, or MYC-HSF1 ChIP-qPCR analyses showed that SP1 or HSF1 signals were less enriched at the promoter of FOXM1 in Cu-stressed group compared with the control ( Figures 8 C2-8C4), and Cu overload significantly up-regulated expression of HSF1 negative target BAX 44 , 45 while significantly down-regulated expressions of HSF1 positive target CDC6 and CKS1B 46 and SP1 positive targets CDC25A 47 and MYCA 48 ( Figure 8 D).…”