Abstract
The biological role of interleukin 6 (IL-6) molecules in human B cell tumorigenesis was studied by using an episomal expression vector, pHEBoSV-IL6, to introduce stably the human IL-6 gene into human Epstein Barr virus (EBV)-transformed B lymphoblasts. The gene was present in the IL-6-transfected cells in a high copy number and was efficiently expressed, resulting in the secretion of consistent levels of IL-6 molecules. The constitutive expression of the IL-6 gene led to an altered pattern of growth and to a malignant phenotype, as shown by clonogenicity in to an altered pattern of growth and to a malignant phenotype, as shown by clonogenicity in soft agar cultures and tumorigenicity in nude mice. These data suggest that the combined action of EBV, which exerts an immortalizing function, and of the growth-promoting activity of IL-6 molecules, can give rise to fully transformed B cell tumors in immunodeficient subjects.
MeSH Terms
Animals
B-Lymphocytes/cytology,microbiology
Blotting, Northern
Cell Line, Transformed
Cell Transformation, Neoplastic/genetics
Cell Transformation, Viral
Female
Gene Expression
Herpesvirus 4, Human/genetics
Interleukin-6/biosynthesis,genetics
Mice
Mice, Nude
Neoplasm Transplantation
Plasmids
Transcription, Genetic
Transfection
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Scala G
Dipartimento di Biochimica e Biotecnologie Mediche, II Facoltà di Medicina, Napoli, Italy.
Quinto I
Ruocco M R
Arcucci A
Mallardo M
Caretto P
Forni G
Venuta S
References (21)
21 references, click to expand
-
Anti-beta-interferon antibodies inhibit the increased expression of HLA-B7 mRNA in tumor necrosis factor-treated human fibroblasts: structural studies of the beta 2 interferon involved.
Proc Natl Acad Sci U S A. 1986 Dec;83(23):8957-61
PMID: 3538015
-
Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas.
Proc Natl Acad Sci U S A. 1986 Dec;83(24):9679-83
PMID: 2948184
-
Identification of the human 26-kD protein, interferon beta 2 (IFN-beta 2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor.
J Exp Med. 1987 Mar 1;165(3):914-9
PMID: 3493322
-
Autocrine growth function of human interleukin 1 molecules on ROHA-9, an EBV-transformed human B cell line.
J Immunol. 1987 Apr 15;138(8):2527-34
PMID: 2435800
-
Pathogenesis of Burkitt lymphoma: expression of an activated c-myc oncogene causes the tumorigenic conversion of EBV-infected human B lymphoblasts.
Cell. 1987 Apr 24;49(2):161-70
PMID: 3032447
-
The role of interferon-beta 1 and the 26-kDa protein (interferon-beta 2) as mediators of the antiviral effect of interleukin 1 and tumor necrosis factor.
J Immunol. 1987 Sep 15;139(6):1867-72
PMID: 3305707
-
Monocyte-derived human B-cell growth factor identified as interferon-beta 2 (BSF-2, IL-6).
Science. 1988 Jan 29;239(4839):502-4
PMID: 2829354
-
A new childhood T-cell lymphoma established in nude mice and in vitro.
Cancer Res. 1988 Mar 1;48(5):1312-8
PMID: 3257718
-
The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells.
J Exp Med. 1988 Feb 1;167(2):332-44
PMID: 3258006
-
The biology of interleukin-6.
Blood. 1989 Jul;74(1):1-10
PMID: 2473791
-
IgG1 plasmacytosis in interleukin 6 transgenic mice.
Proc Natl Acad Sci U S A. 1989 Oct;86(19):7547-51
PMID: 2798426
-
Selective extraction of polyoma DNA from infected mouse cell cultures.
J Mol Biol. 1967 Jun 14;26(2):365-9
PMID: 4291934
-
Autocrine secretion and malignant transformation of cells.
N Engl J Med. 1980 Oct 9;303(15):878-80
PMID: 7412807
-
Human cutaneous T cell lymphoma and leukemia cell lines produce and respond to T cell growth factor.
J Exp Med. 1981 Nov 1;154(5):1403-18
PMID: 6975346
-
New method for detecting cellular transforming genes.
Science. 1982 Dec 10;218(4577):1122-5
PMID: 6293052
-
Soluble factor requirements for the autostimulatory growth of B lymphoblasts immortalized by Epstein-Barr virus.
J Exp Med. 1984 May 1;159(5):1554-9
PMID: 6325575
-
Accessory cell function of human B cells. I. Production of both interleukin 1-like activity and an interleukin 1 inhibitory factor by an EBV-transformed human B cell line.
J Exp Med. 1984 Jun 1;159(6):1637-52
PMID: 6327874
-
"A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum.
Anal Biochem. 1984 Feb;137(1):266-7
PMID: 6329026
-
A vector that replicates as a plasmid and can be efficiently selected in B-lymphoblasts transformed by Epstein-Barr virus.
Mol Cell Biol. 1985 Feb;5(2):410-3
PMID: 2983194
-
Multiple monoclonal B cell expansions and c-myc oncogene rearrangements in acquired immune deficiency syndrome-related lymphoproliferative disorders. Implications for lymphomagenesis.
J Exp Med. 1986 Dec 1;164(6):2049-60
PMID: 3491176
-
Electric field-mediated DNA transfer: transient and stable gene expression in human and mouse lymphoid cells.
Mol Cell Biol. 1986 Feb;6(2):703-6
PMID: 3466022