Loss of functional pRB is not a ubiquitous feature of B-cell malignancies

Abstract

Summary Human cancers frequently sustain genetic mutations that alter the function of their G1 cell cycle control check point. These include changes to the retinoblastoma gene and to the genes that regulate its phosphorylation, such as the cyclin-dependent kinase inhibitor p16 INK4a . Altered expression of retinoblastoma protein (pRb) is associated with non-Hodgkin's lymphoma, particularly centroblastic and Burkitt's lymphomas. pRb is expressed in normal B-cells and its regulatory phosphorylation pathway is activated in response to a variety of stimuli. Since human B-lymphoma-derived cell lines are often used as in vitro model systems to analyse the downstream effects of signal transduction, we examined the functional status of pRb in a panel of human B-cell lines. We identified eleven cell lines which express the hyperphosphorylated forms of pRb. Furthermore, we suggest that the pRb protein appears to be functional in these cell lines.

Mechanisms involved in Burkitt’s lymphoma tumor formation

“…These results might suggest that the pRb pathway is inactivated in a fraction of BL lines and tumors. Other groups have shown, however, that pRb appears functional and normally expressed and phosphorylated in BL [81]. Supporting this notion, we found that pRb readily interacts with E2F family members in different BL cell lines regardless of EBV status [82].…”

Heterogeneous Abnormalities of CCND1 and RB1 in Primary Cutaneous T-Cell Lymphomas Suggesting Impaired Cell Cycle Control in Disease Pathogenesis

“…In this study, RB1 protein expression was identified in most C-ALCL, lymphomatoid papulosis, and transformed MF cases, but not in inflammatory dermatosis. Previous IHC studies have also revealed the presence of RB1 protein expression in tumour cells in relapsing Hodgkin's disease (Amini et al, 2002), adult T-cell leukemia/lymphoma (Nakayama et al, 2000), B-cell lymphomas (Sinclair and Frost 1999), and MALT lymphoma (Stefanaki et al, 1998). The IF8 antibody mainly recognizes the phosphorylated form of RB1 protein, which tends to accumulate in highly proliferating dividing cells such as human colorectal cancer (www.scbt.com), whereas in inflammatory dermatosis such as psoriasis and lichen planus the hypophosphorylated RB1 protein is mainly expressed and therefore not detected by IHC with IF8 antibody.…”

Gene-expression analysis identifies novel RBL2/p130 target genes in endemic Burkitt lymphoma cell lines and primary tumors

“…2 All subtypes of BL are characterized by translocation of genetic material between the long arm of chromosome 8 (8q24) and the immunoglobulin heavy chain region on chromosome 14, resulting in t (8;14). The translocation may infrequently occur between 8q24 and the kappa light chain locus on chromosome 2 (t (2,8)) or between 8q24 and the lambda light chain locus on chromosome 22 (t (8,22)). Regardless of which of these translocations occurs, the result is deregulation of the oncogene c-myc.…”

“…8 The retinoblastoma family is composed of 3 members, pRb/p105, p107, and pRb2/p130. 9 Many of the sequence similarities among these genes reside in a homologous functional domain known as the pocket region.…”