Overexpression of human 27 kDa heat shock protein in laryngeal cancer cells confers chemoresistance associated with cell growth delay

Abstract

HSP27 overexpression induced cellular resistance to heat shock at 45 degrees C for 1 h as well as against several cytotoxic agents, including cisplatin, staurosporin and H(2)O(2). However, no difference in sensitivity to irradiation or serum starvation was found. Moreover, HSP27 overexpressing Hep-2 cells showed a delayed cell growth, compared to control cells. To determine if the decreased cell proliferation in HSP27 overexpressing cells contributed to chemoresistance, control Hep-2 cells were synchronized at the late G1 phase by treatment with mimosine. The synchronized Hep-2 cells were resistant to cisplatin and H(2)O(2), but not to irradiation or serum starvation, correlating the protection effect shown in HSP27 overexpressing cells. These results suggest that the overexpression of HSP27 in Hep-2 cells confers chemoresistance which is associated with the delay in cell growth. We also propose that the stabilization of F-actin observed in Hep-2/hsp27 cells is partly related to the delay in cell cycle progression, by showing that the induction of actin polymerization in Hep-2/neo cells results in the retardation of cell growth as well as a cytoprotective effect as observed in Hep-2/hsp27.

Heat shock protein 70 silencing enhances apoptosis inducing factor-mediated cell death in hepatocellular carcinoma HepG2 cells

“…3,22 Overexpression of HSP70s confers to chemoresistance in human cancer cells, but HSP70 inhibition suppresses tumor growth. 23,24 Therefore, we HSP70 shRNA enhances AIF-induced cell death The efficiency of HSP70 gene silencing was confirmed at mRNA and protein levels by RT-PCR and Western blot assays. β-actin was used as internal control.…”

The heat shock proteins as targets for radiosensitization and chemosensitization in cancer

“…51 Additionally, small oligomers of Hsp27 stabilize polymerized, or F-actin, exerting a protective effect through the cytoskeleton. [52][53][54] The small oligomers have also been found to play a role in protein degradation through the ubiquitinproteasome pathway under cellular stress. 4,55 Lastly, small Hsp27 oligomers, which favor the degradation of I-kB and consequently enhance NF-kB activity, contribute to its anti-apoptotic qualities as well.…”

“…For instance, the protein is reportedly overexpressed in clinical specimens from oral squamous cell carcinoma, oropharyngial and laryngial cancers. 53 Hsp27 has also been shown to provide useful prognostic information for cancer patients. 37 For example, high Hsp27 expression was related to poor prognosis following surgery as well as resistance to adjuvant therapy across several cancer types including breast cancer, gastric cancer, osteosarcoma, prostate cancer, head and neck, and colon cancer.…”

“…37 For example, high Hsp27 expression was related to poor prognosis following surgery as well as resistance to adjuvant therapy across several cancer types including breast cancer, gastric cancer, osteosarcoma, prostate cancer, head and neck, and colon cancer. 45,53 Hsp27 expression can yield prognostic information about chemotherapy response as well. For example, high Hsp27 expression in childhood leukemia can predict a poor response to vincristine.…”

Proteomic analysis of protein expression in human tonsillar cancer differentially expressed proteins characterize human tonsillar cancer

“…Furthermore, Muzio and coworkers postulated that a reduced expression of HSP 27 is an early marker of poor prognosis and useful in identifying aggressive biological behaviour in oral squamous cell cancer [26]. It has been implicated that down-regulation of HSP 27 may confer to chemo-resistance associated with cellular growth delay [27]. Consistent with our findings of up-regulated HSP 27 in tonsillar cancer, other investigations on oral cancer have found a similar expression pattern of this protein [3,17,18].…”