Apoptosis is normally kept under strict control by a range of regulators and inhibitors, and loss of this regulation strongly directs tumour progression. The novel RBBP6 gene has been implicated in apoptosis due to its ability to bind both p53 and Rb, as well as its structural and functional affiliation to ubiquitin and E3 ligases. RBBP6 has already been implicated as an important marker for cancer diagnosis and many studies have investigated its suitability as a potential genetic target for cancer treatment. This study endeavoured to assess the transcription and expression patterns and levels of the three isoforms of RBBP6 in colon cancer and to evaluate its potential role in apoptosis. Colorimetric and fluorescent in situ hybridisation was used to localise the mRNA and the different RBBP6 mRNA transcripts in normal and cancerous colon tissue. Immunohistochemistry was used to localise different RBBP6 isoforms in normal and cancerous tissues. All the RBBP6 transcripts were found to be up-regulated in cancerous tissues, and the expression levels of the RBBP6-1 and RBBP6-3 (DWNN) proteins were also found to be increased in cancerous structures. Higher levels of apoptosis were detected in the same regions as those that showed increased expression of RBBP6-3 transcript and protein, whereas Bcl-2 was down-regulated in these areas. In contrast we observed an increase in Bcl-2 levels in areas where RBBP6-3 was down-regulated. These results suggest that the RBBP6-3 isoform may be involved in promoting apoptosis in cancerous cells.
Keywords: Apoptosis; Colon cancer; DWNN; RBBP6; Ubiquitin.