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Expression of HSP60 in colorectal cancer and implication in chemotherapeutic responses
Background
Heat shock protein 60 (HSP60), also known as chaperonin and HSPD1, belongs to the heat shock protein family. The HSP60 protein is an intramitochondrial chaperonin protein that takes part in post-translational modification for the client proteins with other family members. Recently, HSP60 has been reported to have a possible role as an oncogenic protein in various cancer types, both in their development and progression and also in the metabolism of certain drugs. The aim of the current study was to explore HSP60 expression at transcript and protein levels in clinical cohort and tissue microarray of colorectal cancers and its role in chemotherapeutic responses in colorectal cancer cell lines.
Methods
The expression of HSP60 transcript was carried out on a clinical cohort of fresh frozen samples harvested after surgical resection of colorectal cancer (n=174). Levels of HSP60 transcripts were obtained by real time quantitative PCR (qPCR) and was analysed in comparison with clinical and pathological information to investigate its clinical implication. HSP60 protein was detected by way of immunohistochemistry on a tissue microarray of colorectal cancer. A colorectal TCGA dataset with information on chemotherapeutic responses was analysed on the clinical relevance of expression of HSP60 (200806_s_at) and patient’s response to chemotherapies and also with various chemodrugs. Human colorectal cancer cell lines, RKO and HRT18 were selected to generate HSP60 knockdown cell submodels by way of HSP60 siRNA. These cell models were used to test their responses to chemotherapeutic agents.
Results
Colorectal tumour tissues had raised levels of HSP60 transcript (p 0.05) and 5-FU (p>0.05). In our in vitro cell models, knockdown HSP60 from the colorectal cancer cells rendered them more sensitive to selective drugs tested. For example, IC50s of Oxaliplatin for HRT18 cells was 4.5mM in the control wild type cells, compared with 0.54mM in HSP60 knockdown cells. These collectively suggest that levels of HSP60 in colon cancer may have important indication to patient’s drug treatment responses.
Conclusions
HSP60 expression has an aberrant expression pattern at both transcript and protein levels in clinical colorectal cancers and has important indications to both disease progression and therapeutic responses to drugs.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
All authors have declared no conflicts of interest.
