Abstract
RBBP6 is a novel gene encoding splicing-associated proteins. There are 3 protein isoforms (isoforms 1-3). RBBP6 isoforms 1 has been shown to interact with both p53 and Rb. It also plays a role in the induction of apoptosis and the regulation of the cell cycle. The expression of RBBP6 has been documented in several cancers but RBBP6 expression in cervical cancer has not been well studied. The aim of this study was to establish expression levels and tissue distribution of the RBBP6 gene products at both protein and messenger RNA (mRNA) levels in cervical cancer by immunocytochemistry and in situ hybridization (ISH). A link between RBBP6 expression, apoptosis, and cervical cancer progression was also investigated. RBBP6 mRNA was expressed in the nuclei and cytoplasm of normal and tumour cervical epithelium. In general, expression was high in the cytoplasm and nuclei of moderately differentiated and invasive carcinoma. Immunolabelling results were confirmed by image analysis and ISH experiments. Apoptosis assays using TUNEL correlated with the expression of the RBBP6 gene in all examined cases. This is the first report on the abundant expression of RBBP6 in cervical cancer and its involvement in the malignant progression of cervical cancer. Because of the high expression and corresponding pro-apoptotic activity observed in cervical cancer cells in this study, we suggest that RBBP6 is involved in the malignant progression of cervical cancer. RBBP6 proteins can therefore be targeted for therapeutic interventions against cervical cancer.
Highlights
Cervical cancer has emerged as a leading cause of cancerrelated mortalities in South African women.[1]
The Fluorescent in situ hybridization (FISH) results showed a progressive decrease in the transcription of the retinoblastoma-binding protein 6 (RBBP6) messenger RNA (mRNA), as indicated in our previous work[6]; RBBP6 variant 3-mRNA transcription was lost in tumours (Figure 2C)
RBBP6 interacts with tumour suppressor proteins p53 and Rb, suggesting that it is involved in apoptosis
Summary
Cervical cancer has emerged as a leading cause of cancerrelated mortalities in South African women.[1]. P53, has been documented to be negatively regulated by retinoblastoma-binding protein 6 (RBBP6) and increased RBBP6 expression results in tumourigenesis, whereas its knockdown results in cell growth arrest and apoptosis. This resulted in retarded growth in mice.[4] RBBP6 is a multi-domain 250 kDa nuclear protein containing a conserved N-terminal DWNN domain.[5] The RBBP6 proteins are translated from 2 major transcripts of 1.1 and 6.1 kb. The increased understanding of the mechanisms of apoptosis has led to novel therapeutic approaches that may be used to stimulate tumour cells to undergo apoptosis
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