Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer

Abstract

BackgroundEnhanced activity of histone deacetylases (HDAC) is associated with more aggressive tumour behaviour and tumour progression in various solid tumours. The over-expression of these proteins and their known functions in malignant neoplasms has led to the development of HDAC inhibitors (HDI) as new anti-neoplastic drugs. However, little is known about HDAC expression in renal cell cancer.MethodsWe investigated the expression of HDAC 1, 2 and 3 in 106 renal cell carcinomas and corresponding normal renal tissue by immunohistochemistry on tissue micro arrays and correlated expression data with clinico-pathological parameters including patient survival.ResultsAlmost 60% of renal cell carcinomas expressed the HDAC isoforms 1 and 2. In contrast, HDAC 3 was only detected in 13% of all renal tumours, with particular low expression rates in the clear cell subtype. HDAC 3 was significantly higher expressed in pT1/2 tumours in comparison to pT3/4 tumours. Expression of class I HDAC isoforms correlated with each other and with the proliferative activity of the tumours. We found no prognostic value of the expression of any of the HDAC isoforms in this tumour entity.ConclusionClass I HDAC isoforms 1 and 2 are highly expressed in renal cell cancer, while HDAC 3 shows low, histology dependent expression rates. These unexpected differences in the expression patterns suggests alternative regulatory mechanisms of class I HDACs in renal cell cancer and should be taken into account when trials with isoform selective HDI are being planned. Whether HDAC expression in renal cancers is predictive of responsiveness for HDI will have to be tested in further studies.

A novel HDAC inhibitor OBP-801 and a PI3K inhibitor LY294002 synergistically induce apoptosis via the suppression of survivin and XIAP in renal cell carcinoma

“…Recent clinical trials have indicated that HDAC inhibitors enhance the antitumor activities of several conventional chemotherapeutic and molecular-target drugs (25)(26)(27). Additionally, a previous study showed that HDACs were highly expressed in RCC, suggesting that HDAC inhibitors may be effective on RCC (28). Recently, the mTOR inhibitors everolimus and temsirolimus have been clinically used as a treatment against RCC, but are not curative.…”

HDAC2 regulates cell proliferation, cell cycle progression and cell apoptosis in esophageal squamous cell carcinoma EC9706 cells

“…A high level of HDAC2 is an independent prognostic factor for various types of tumors, including oral, ovarian, endometrial and gastric cancers (6,10,15). Fritzsche et al (25) reported a 60% increase in HDAC2 expression in renal cancer. Adams et al found that HDAC2 was also highly expressed in Hodgkin's lymphoma (26).…”

Histone deacetylases and the immunological network: implications in cancer and inflammation

“…For example, HDAC1, 2 and 3 are overexpressed in ovarian and endometrial carcinomas (Weichert et al, 2008a), prostate (Weichert et al, 2008b) and renal cancer (Fritzsche et al, 2008). HDAC1 is overexpressed in cancers of the breast , colon (Wilson et al, 2006) and pancreas (Wang et al, 2009b), whereas HDAC3 expression is increased in colon cancer (Wilson et al, 2006).…”