Hsp27 overexpression inhibits doxorubicin–induced apoptosis in human breast cancer cells

Abstract

Previously we demonstrated that heat shock protein 27 (hsp27) overexpression confers resistance to the chemotherapeutic agent doxorubicin in MDA-MB-231 breast cancer cells. Since induction of apoptosis is one underlying mechanism of chemotherapeutic drug action, we investigated the effect of hsp27 overexpression on doxorubicin-induced apoptosis, finding that hsp27 protects MDA-MB-231 cells from apoptosis. We also examined expression of the doxorubicin target, topoisomerase II (topo II), in control and hsp27-overexpressing stable transfectants, as topo II expression is important for both drug sensitivity and the initiation of apoptosis by doxorubicin. The relative levels of both topo IIalpha and beta were higher in the controls than the hsp27-overexpressing clones, suggesting that the apoptotic protective effect of hsp27 overexpression in MDA-MB-231 cells is associated with altered topo II expression.

Hsp-27 induction requires POU4F2/Brn-3b TF in doxorubicin-treated breast cancer cells, whereas phosphorylation alters its cellular localisation following drug treatment

“…Therefore, increased Brn-3b TF in breast cancer cells can control distinct aspects of cell growth and behaviour, depending on target genes that it regulates under different cellular conditions. Previous studies had shown that Hsp-27 controls the survival and behaviour of breast cancer cells, and increased Hsp-27 is associated with enhanced anchorage-dependent and independent growth, tumour invasion and resistance to chemotherapeutic drugs (Hansen et al 1999;. The increased expression of Hsp-27 in Brn-3b-positive Dox-treated cells is not surprising since we previously showed that this transcription regulator is necessary for maximal stimulation of Hsp-27 in breast cancer cells (Lee et al 2005).…”

Inhibition of heat shock protein 27 (HspB1) tumorigenic functions by peptide aptamers

“…Expression of Hsp27 is upregulated in numerous types of tumors (particularly breast, colon, ovarian and head and neck tumors) and promotes unfavorable outcome (Ciocca and Calderwood, 2005). Overexpression of this protein is frequently associated with increased resistance to radiotherapy and to anti-cancer drugs, such as cisplatin, doxorubicin and etoposide (Hansen et al, 1999;Kim et al, 2007;Zhang and Shen, 2007). Others and we have shown that targeting Hsp27 by antisense strategy increases cancer cell death in vitro and in vivo (Aloy et al, 2008;Matsui et al, 2009).…”

“…Hsp27 has been reported to induce high resistance to some of the drugs used in chemotherapy (Hansen et al, 1999;Kim et al, 2007;Zhang and Shen, 2007). To assess effects of PAs on drug response, HeLa cells transfected with PA11 or PA50 were treated for 18 h with cisplatin or doxorubicin.…”

Binding of Caspase-3 Prodomain to Heat Shock Protein 27 Regulates Monocyte Apoptosis by Inhibiting Caspase-3 Proteolytic Activation

“…In human monocytes heat shock-induced expression of Hsp70 has been correlated with monocyte survival (21). High levels of Hsp27 are a marker for increased malignancy in breast cancer (22), and Hsp27 overexpression prevents apoptosis by associating with cytochrome c, resulting in the inhibition of caspase-9 (23). In addition, ␣B-crystallin has been suggested to act as a negative regulator of apoptosis during skeletal muscle development by inhibiting caspase-3 activation (24).…”