Expression of the c‐fgr related transcripts in epstein‐barr virus‐associated malignancies

Abstract

The proto-oncogene c-fgr is expressed at high levels in cell lines derived from lymphomas which are infected with Epstein-Barr virus (EBV) (Cheah et al., 1986). mRNA extracted directly from biopsies of EBV-infected tissues was analyzed on Northern blots to determine if c-fgr is expressed during lympho-proliferations induced in vivo by EBV and in nasopharyngeal carcinoma (NPC), the epithelial malignancy associated with the virus. Elevated levels of c-fgr expression were detected in all EBV-positive lympho-proliferations in vivo but not in cell lines established by EBV infection in vitro. This indicates that the induction of the c-fgr proto-oncogene is not an essential component of EBV-induced transformation. Although no c-fgr expression was detected in EBV-positive or -negative epithelial cell lines, the 3.0-kb c-fgr mRNA was detected at low levels in mRNA obtained from NPC biopsy specimens. However, NPC tissue, after passage in nude mice (which eliminates infiltrating lymphoid and myeloid cells) did not contain the 3.0-kb c-fgr mRNA. The absence of expression of c-fgr in the malignant epithelial cells infected with EBV contrasts with the elevated level of the proto-oncogene in EBV-infected lymphoma tissue and cell lines established from lymphomas. This suggests differences in the expression of cellular functions in EBV-induced malignancies of these 2 distinct cell types.

Comparison of gene expression profiles of lymphoma cell lines from transformed follicular lymphoma, Burkitt's lymphoma and de novo diffuse large B‐cell lymphoma

“…Nevertheless, the observed difference is potentially a reflection of fundamental genetic and biological characteristics of each lymphoma subtype, since the cell lines used presumably share gene expression programs associated with the properties of B cells, resistance to chemotherapeutic agents and rapid proliferation in the tissue culture environment. The selection of FGR, the expression of which was previously shown to be induced by EBV, 17,18) with the highest predictive strength as the marker for EBV(+)BL supports the validity of this approach. Another advantage of the study of cell lines over that of clinical materials is the elimination of the profile of nonmalignant components contaminating lymphoma specimens, although this may conversely lead to missing information on tumor cell-reactive cell interaction.…”

Modulation of B-cell exosome proteins by gamma herpesvirus infection

“…LMP1 has been shown to up-regulate HLA proteins, and their enriched secretion into exosomes may modulate viral entry or immune recognition (22)(23)(24). Furthermore, the EBV/LMP1 exosomes contained multiple kinases including the TNF receptor-associated factor 2 and NF-κB-inducing kinase (TNIK) (25), the fgr kinase, which has been linked to EBV infection (26), and the protein 85 (p85) regulatory subunit of PI3K, a protein recently shown to be induced into lipid rafts by LMP1 expression (16). Additional proteins previously shown to be up-regulated by LMP1, including intercellular adhesion molecule 1 and ezrin, also were increased in the EBV exosomes (13,27) (Figs.…”

Regulation of C‐FGR proto‐oncogene expression in epstein‐barr virus infected B‐cell lines

“…However, Sharp et al (1989) found that the P3HR-1 cell line, which is also infected with HR-1 virus, expressed only low levels of clfgr mRNA. In addition, Klein et al (1988) found that 2 B-lymphoblastoid cell lines (B-LCL) derived by EBVinfection of normal B-lymphocytes did not express elevated levels of clfgr mRNA, although this contradicted an earlier finding of Cheah et al (1986).…”

“…A role for Fgr in the EBV-induced immortalization of Blymphocytes has been suggested by the observation that c-jgr mRNA levels, which are low in EBV-negative BL cell lines, are considerably elevated following EBV conversion of EBVnegative BL cell lines (Brickell and Patel, 1988;Klein et al, 1988;Cheah et al, 1986) with the B95-8 strain of EBV. EBVpositive BL biopsies and cell lines also express elevated levels of c-fgr mRNA.…”

“…EBVpositive BL biopsies and cell lines also express elevated levels of c-fgr mRNA. Arguing against a role for Fgr in the events leading to B-lymphocyte immortalization by EBV, Klein et al (1988) and Cheah et al (1986) found that a long-established BL cell line converted with the non-immortalizing HR-1 strain of EBV expressed elevated levels of c-fgr mRNA. However, Sharp et al (1989) found that the P3HR-1 cell line, which is also infected with HR-1 virus, expressed only low levels of clfgr mRNA.…”