Missing expression of pRb2/p130 in human retinoblastomas is associated with reduced apoptosis and lesser differentiation

PURPOSE: Although the retinoblastoma gene (RB/p105) has been intensely investigated as a prototype suppressor gene in humans, mutational data on the Rb family member pRb2/p130 (p130) has only recently been reported. A protective role against apoptosis has been suggested for pRb/p105, both in vitro and in vivo. However, only limited information is available on the role of pRb2/p130 in controlling apoptosis. The purpose of this study was to determine the extent of a role of this gene in the neoplasms that give the Rb family its name. METHODS: Forty-two human retinoblastomas were retrospectively examined by immunohistochemical labeling of the Rb-related proteins and the results compared with cellular kinetic characteristics: the apoptotic index (AI) and the mitotic index (MI). RESULTS: The retinoblastomas that did not express p130 showed a significantly lower AI than those that expressed p130. This result was also supported by flow cytometry on a human Saos-2 cell line that was transiently transfected with RB2/p130. The p130(-) tumors displayed a lesser degree of differentiation than the p130(+) ones. CONCLUSIONS: These observations give evidence that expression of p130 is inversely correlated with higher rates of apoptosis in human retinoblastomas and give an additional example of this regulator's role in cellular differentiation.