Expression of p27 (KIP1) and cell proliferation in human retina and retinoblastoma
Kase, S.; Yoshida, K.; Ohgami, K.; Shiratori, K.; Harada, T.; Ohno, S.
Anticancer Research 25(6b): 3843-3846
2005
ISSN/ISBN: 0250-7005 PMID: 16309169 Document Number: 587784
Background: Retinoblastoma is a rare cancer of the eye, in which biallelic inactivation of the retinoblastoma gene is a hallmark. Although retinoblastoma protein (Rb) and p27(KIP1) block the cell cycle transition from G1- to S-phase, the interaction has not been confirmed in vivo. The aim of this study was to examine the correlation between the expression of p27(K[PI) and cell proliferation in human retina and retinoblastoma.Materials and Methods: Human retinoblastoma, surgically removed, was fixed by 4% paraformaldehyde. Then, paraffin-embedded tissue sections were examined using immunohistochemistry with antip27(KIP1) and anti-proliferating cell nuclear antigen (PCNA) antibodies.Results: Retinoblastoma tissue was adjacent to the normal retina in which tumor cells with homogeneous nuclei proliferated and it was impossible to identify the layer structure of the inner nuclear layer (INL) and the outer nuclear layer (ONL). In normal retina, PCNA-positive nuclei were not observed, whereas nuclear immunoreactivity for PCNA was detected in a variety of tumor cells. Many p27(KIP1) -positive nuclei were detected in INL and ONL, while p27(KIP1) immunoreactivity was not detected in retinoblastoma cells.Conclusion: The correlation between disappearance of p27(KIP1) and induction of proliferation activity suggests that functional loss of Rb leads to down-regulation of p27(K[P1) and uncontrolled retinal cell proliferation.