Expression and function of retinoblastoma binding protein 6 (RBBP6) in human lung cancer.

Retinoblastoma binding protein 6 (RBBP6) interacts with both p53 and pRb, and has been identified as an E3 ubiquitin ligase due to the presence of a RING finger domain. RBBP6 promotes the degradation of p53, thereby increasing cell proliferation. However it is not known whether RBBP6 is expressed in lung cancer, or interacts with p53 and pRB to modulate the proliferation or apoptosis of lung cancer cells. As assessed by immunohistochemistry, RBBP6 and p53 proteins were overexpressed in lung adenocarcinomas and lung squamous cell carcinomas. Expression of RBBP6 mRNA in lung tumor tissue was demonstrated by quantitative RT-PCR and fluorescence in situ hybridization. Expression of RBBP6 mRNA was low in poorly differentiated tumors but high in well-differentiated tumors. Bronchoalveolar carcinomas showed intense RBBP6 mRNA hybridization in the cytoplasm of cells undergoing mitosis, supporting the association between RBBP6 expression and cell proliferation. By qRT-PCR, RBBP6 mRNA expression was 1.6 fold higher, whereas p53 mRNA expression was 2.9 fold lower in lung tumors compared with normal lung tissue. Transfection of lung adenocarcinoma and squamous cell carcinoma cells with RBBP6 siRNA decreased RBBP6 mRNA expression, whereas transfection with p53 siRNA increased RBBP6 mRNA expression. Treatment with RBBP6 siRNA increased the ratio of Bax/Bcl2 mRNA, suggesting that RBBP6 may have an anti-apoptotic function in lung cancer cells. This is the first report that RBBP6 mRNA and "its protein products" are expressed in subtypes of human lung cancer. RBBP6 may be involved in the degradation of p53, thereby enhancing cell proliferation and inhibiting apoptosis in lung cancer.