title: Expression of p27(KIP1) and cell proliferation in human retina and retinoblastoma.
abstract: 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(KIP1) and cell proliferation in human retina and retinoblastoma.
  
  
  METHODS
  Human retinoblastoma, surgically removed, was fixed by 4% paraformaldehyde. Then, paraffin-embedded tissue sections were examined using immunohistochemistry with anti-p27(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.
  
  
  CONCLUSIONS
  The correlation between disappearance of p27(KIP1) and induction of proliferation activity suggests that functional loss of Rb leads to down-regulation of p27(KIP1) and uncontrolled retinal cell proliferation.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, N15 W7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kase
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yoshida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ohgami
authors.forename: Kenji
authors.initials: K
authors.lastname: Shiratori
authors.forename: Takayuki
authors.initials: T
authors.lastname: Harada
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ohno
mesh_terms: D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D005260:Female; D016193:G1 Phase / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D019572:Retinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D012175:Retinoblastoma / Q000378:metabolism* / Q000473:pathology; D016196:S Phase / Q000502:physiology
chemical_list: C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018809:Proliferating Cell Nuclear Antigen; D050760:Cyclin-Dependent Kinase Inhibitor p27