Expression of retinoblastoma gene product (pRb) in mantle cell lymphomas - Correlation with cyclin D1 (PRADI/CCND1) mRNA levels and proliferative activity

P Jares, E Campo, M Pinyol, F Bosch, R Miquel, PL Fernandez, M SanchezBeato, F Soler, A PerezLosada, Iracema Nayach, C Mallofre, MA Piris, E Montserrat, A Cardesa

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Abstract

Mantle cell lymphomas (MCLs) are molecularly characterized by bcl-1 rearrrangement and constant cyclin DI (PRAD-1/CCND1) gene overexpression, Cyclin DI is a GI cyclin that participates in the control of the cell cycle progression by interacting with the retinoblastoma gene product (pRb), Inactivation of the Rb tumor suppressor gene has been implication the development of different types of human tumors including some high grade non-Hodgkin's lymphomas. To determine the role of the retinoblastoma gene in the pathogenesis of MCLs and its possible interaction with cyclin DI, pRb expression was examined in 23 MCLs including 17 typical and 6 blastic variants by immunohistochemistry and Western blot Rb gene structure was studied in 13 cases by Southern blot, Cytogenetic analysis was performed in 5 cases, The results were compared with the cyclin D1 mRNA levels examined by Northern analysis, and the proliferative activity of the tumors was measured by Ki-67 growth fraction and flow cytometry. pRb was expressed in all MCLs. The expression varied from case to case (mean, 14.1% of positive cells; range, 1.3 to 42%) with a significant correlation with the proliferative activity, of the tumors (mitotic index r = 0.85; Ki-67 r = 0.7; S phase = 0.73), Blastic variants showed higher numbers of PRb-positive cells (mean, 23%) than the typical cases (10%; P <0.005) by, immunohistochemistry and, concordantly, higher levels of expression by Western blot, In addition, the blastic cases also had nit increased expression of the phosphorylated protein, No alterations in Rb gene structure were observed by Southern blot analysis, Cyclin D1 mRNA levels were independent of pRb expression and the proliferative activity of the tumors, These findings suggest that pRb in MCLs is normally regulated in relation to the proliferative activity of the tumors, Cyclin DI overexpression may play a role its the maintenance of cell proliferation by overcoming the suppressive growth control of pRb.

Original languageEnglish
Pages (from-to)1591-1600
Number of pages10
JournalAm. J. Pathol.
Volume148
Issue number5
Publication statusPublished - May 1996

Keywords

  • LYMPHOCYTIC LYMPHOMA
  • INTERMEDIATE DIFFERENTIATION
  • CENTROCYTIC LYMPHOMA
  • OVEREXPRESSION
  • PROTEIN
  • BCL-1
  • REARRANGEMENT
  • TRANSLOCATION
  • FIBROBLASTS
  • PROGRESSION

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