Retinoblastoma (Rb) gene product expression in lymphomas. Correlation with Ki67 growth fraction.
The retinoblastoma susceptibility gene (Rb) has been characterized as a tumour suppressor gene. Rb protein is involved in cell-cycle control, regulating gene transcription. The absence of Rb protein in inherited retinoblastoma has been proved to be the result of inactivation of both Rb alleles through mutation or deletion, according to the general model for suppressor genes. The frequent detection of Rb gene alterations in human tumours (retinoblastoma, osteosarcoma, bladder carcinoma, small-cell lung carcinoma) and the correlation with clinical outcome found in some tumours prompted us to study Rb gene expression in lymphoid tumours in an attempt to determine whether Rb gene expression is related to histological type and degree of aggressivity in human lymphomas. To establish normal levels of Rb protein, its expression was analysed in vitro on cytospin preparations from normal and pokeweed mitogen (PWM) or phytohaemagglutinin (PHA)-stimulated peripheral blood lymphocytes (PBLs), using a monoclonal antibody (PMG3-245). Rb protein expression in vivo was quantified using a computer analysis system (CAS) on frozen sections from reactive and neoplastic lymphoid tissue. As a control of tissue preservation, and to compare Rb expression and growth fraction, the tumours and cells were labelled simultaneously with the Ki67 monoclonal antibody. Normal and stimulated lymphocytes showed a gradual increase of Rb protein during progression of the cell cycle, with a peak in the M phase. G0-G1 cells had no detectable levels of Rb protein, suggesting that the Rb gene may act as a 'status quo' cellular growth fraction control mechanism. In reactive lymphoid tissue, Rb protein was mainly expressed in germinal centres (lymph nodes, tonsils) and cortical thymocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pathology, Instituto Oftálmico (SRS-CAM), Toledo, Spain.
J C
JC
Martínez
M A
MA
Piris
M
M
Sánchez-Beato
R
R
Villuendas
J L
JL
Orradre
P
P
Algara
L
L
Sánchez-Verde
P
P
Martínez
D000911:Antibodies, Monoclonal; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D015870:Gene Expression / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D008214:Lymphocytes / Q000187:drug effects; D008221:Lymphoid Tissue / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010835:Phytohemagglutinins; D011043:Pokeweed Mitogens; D016160:Retinoblastoma Protein / Q000032:analysis* / Q000235:genetics
D000911:Antibodies, Monoclonal; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010835:Phytohemagglutinins; D011043:Pokeweed Mitogens; D016160:Retinoblastoma Protein