The myc Oncogene and Lymphoid Neoplasia: From Translocations to Transgenic Mice

1987 ◽  
pp. 248-251 ◽  
Author(s):  
S. Cory ◽  
A. W. Harris ◽  
W. Y. Langdon ◽  
W. S. Alexander ◽  
L. M. Corcoran ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Myc Oncogene ◽  
Lymphoid Neoplasia

scholarly journals Expression of the c-myc oncogene under control of an immunoglobulin enhancer in E mu-myc transgenic mice.

1987 ◽  
Vol 7 (4) ◽  
pp. 1436-1444 ◽  
Author(s):  
W S Alexander ◽  
J W Schrader ◽  
J M Adams
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice ◽  
B Lymphocyte ◽  
Lymphoid Cells ◽  
Lymphoid Tissues ◽  
Myc Oncogene ◽  
Feedback Model ◽  
B Lymphocyte Development ◽  
B Lymphoid ◽  
Spleen And Lymph Nodes

Transgenic mice bearing a cellular myc oncogene coupled to the immunoglobulin heavy-chain enhancer (E mu) exhibit perturbed B-lymphocyte development and succumb to B lymphoid tumors. To investigate how the enhancer has affected myc expression, we analyzed the structure and abundance of myc transcripts in tissues of prelymphomatous mice and in the lymphomas. Expression of the E mu-myc transgene appeared to be confined largely to B lymphoid cells, being dominant in bone marrow, spleen, and lymph nodes, with no detectable expression in T cells or other hematopoietic lineages examined. The myc transcripts initiated very predominantly at the normal myc promoters, although use of the more upstream myc promoter was accentuated and an enhancer-associated promoter may be used infrequently. The level of E mu-myc transcripts in the preneoplastic lymphoid tissues and in the E mu-myc tumors was not markedly higher than myc RNA levels in proliferating normal lymphocytes. Thus, enforced expression of structurally normal myc transcripts at only a modestly elevated level has profound biological consequences. The absence of detectable endogenous c-myc RNA in any tumor, or in preneoplastic bone marrow, supports a negative feedback model for normal c-myc regulation.

Myc Promotes Tumorigenesis by Supressing Nfkb2.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1422-1422
Author(s):  
Ulrich Keller ◽  
Juergen Huber ◽  
Jonas Nilsson ◽  
Mark Hall ◽  
Christian Peschel ◽  
...  
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
Burkitt Lymphoma ◽  
Transcriptional Repression ◽  
Early Passage ◽  
Transgenic Expression ◽  
Myc Oncogene ◽  
Protein Levels ◽  
Induced Apoptosis

Abstract Rel/NF-kappaB transcription factors are mediators of immune responses, cell survival, and transformation, and are frequently deregulated in cancer. The NF-kappaB2 subunit is associated with chromosomal translocations or deletions in lymphoid malignancies, and deletion of the COOH-terminal ankyrin domain of NF-kappaB2 results in increased lymphocyte proliferation. Here, we report that activation of the Myc oncogene leads to suppression of Nfkb2 expression in early passage mouse embryonic fibroblasts and primary bone marrow-derived B cells. Accordingly, transgenic expression of c-Myc in the Eμ-Myc model of human Burkitt lymphoma results in reduced nfkb2 transcript and NF-kappaB2 p100 and p52 protein levels in pre-cancerous B cells. Nfkb2 expression is further reduced in the majority of Eμ-Myc lymphomas and in human Burkitt lymphoma. Nfkb2 suppression by Myc occurs at least in part by transcriptional repression as shown by promoter studies. To evaluate the relevance of Myc-mediated suppression of Nfkb2 for tumorigenesis, consequences of complete Nfkb2 loss were evaluated in vivo. In pre-cancerous B cells of Myc-transgenic mice, loss of Nfkb2 affects Myc-induced apoptosis while B cell proliferation is unaffected. Deletion of Nfkb2 results in an acceleration of lymphoma development in Eμ-Myc transgenic mice. Therefore, Myc-induced Nfkb2 suppression promotes lymphomagenesis.

The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice

Nature ◽  
1985 ◽  
Vol 318 (6046) ◽  
pp. 533-538 ◽  
Author(s):  
J. M. Adams ◽  
A. W. Harris ◽  
C. A. Pinkert ◽  
L. M. Corcoran ◽  
W. S. Alexander ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Lymphoid Malignancy ◽  
Myc Oncogene

c-Myc-Induced Lymphomagenesis in Transgenic Mice and the Role of the Pvt-1 Locus in Lymphoid Neoplasia

1986 ◽  
pp. 1-8 ◽  
Author(s):  
Jerry M. Adams ◽  
Alan W. Harris ◽  
Wallace Y. Langdon ◽  
Carl A. Pinkert ◽  
Ralph L. Brinster ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Lymphoid Neoplasia

The c-myc oncogene perturbs B lymphocyte development in Eμ-myc transgenic mice

Cell ◽  
1986 ◽  
Vol 47 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Wallace Y. Langdon ◽  
Alan W. Harris ◽  
Suzanne Cory ◽  
Jerry M. Adams
Keyword(s):  
Transgenic Mice ◽  
B Lymphocyte ◽  
Lymphocyte Development ◽  
Myc Oncogene ◽  
B Lymphocyte Development

Expression of the c-myc oncogene under control of an immunoglobulin enhancer in E mu-myc transgenic mice

1987 ◽  
Vol 7 (4) ◽  
pp. 1436-1444
Author(s):  
W S Alexander ◽  
J W Schrader ◽  
J M Adams
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice ◽  
B Lymphocyte ◽  
Lymphoid Cells ◽  
Lymphoid Tissues ◽  
Myc Oncogene ◽  
Feedback Model ◽  
B Lymphocyte Development ◽  
B Lymphoid ◽  
Spleen And Lymph Nodes

Transgenic mice bearing a cellular myc oncogene coupled to the immunoglobulin heavy-chain enhancer (E mu) exhibit perturbed B-lymphocyte development and succumb to B lymphoid tumors. To investigate how the enhancer has affected myc expression, we analyzed the structure and abundance of myc transcripts in tissues of prelymphomatous mice and in the lymphomas. Expression of the E mu-myc transgene appeared to be confined largely to B lymphoid cells, being dominant in bone marrow, spleen, and lymph nodes, with no detectable expression in T cells or other hematopoietic lineages examined. The myc transcripts initiated very predominantly at the normal myc promoters, although use of the more upstream myc promoter was accentuated and an enhancer-associated promoter may be used infrequently. The level of E mu-myc transcripts in the preneoplastic lymphoid tissues and in the E mu-myc tumors was not markedly higher than myc RNA levels in proliferating normal lymphocytes. Thus, enforced expression of structurally normal myc transcripts at only a modestly elevated level has profound biological consequences. The absence of detectable endogenous c-myc RNA in any tumor, or in preneoplastic bone marrow, supports a negative feedback model for normal c-myc regulation.

Quantitative Microscopic Comparison of the Organization of the Lung in Transgenic Mice Expressing Transforming Growth Factor-α (TGF-α)

1996 ◽  
Vol 54 ◽  
pp. 14-15
Author(s):  
C. G. Plopper ◽  
C. Helton ◽  
A. J. Weir ◽  
J. A. Whitsett ◽  
T. R. Korfhagen
Keyword(s):  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Transgenic Mice ◽  
Blood Vessels ◽  
Lung Parenchyma ◽  
Lung Maturation ◽  
Alveolar Air ◽  
Parenchymal Tissue ◽  
Air Space ◽  
Conducting Airways

A wide variety of growth factors are thought to be involved in the regulation of pre- and postnatal lung maturation, including factors which bind to the epidermal growth factor receptor. Marked pulmonary fibrosis and enlarged alveolar air spaces have been observed in lungs of transgenic mice expressing human TGF-α under control of the 3.7 KB human SP-C promoter. To test whether TGF-α alters lung morphogenesis and cellular differentiation, we examined morphometrically the lungs of adult (6-10 months) mice derived from line 28, which expresses the highest level of human TGF-α transcripts among transgenic lines. Total volume of lungs (LV) fixed by airway infusion at standard pressure was similar in transgenics and aged-matched non-transgenic mice (Fig. 1). Intrapulmonary bronchi and bronchioles made up a smaller percentage of LV in transgenics than in non-transgenics (Fig. 2). Pulmonary arteries and pulmonary veins were a smaller percentage of LV in transgenic mice than in non-transgenics (Fig. 3). Lung parenchyma (lung tissue free of large vessels and conducting airways) occupied a larger percentage of LV in transgenics than in non-transgenics (Fig. 4). The number of generations of branching in conducting airways was significantly reduced in transgenics as compared to non-transgenic mice. Alveolar air space size, as measured by mean linear intercept, was almost twice as large in transgenic mice as in non-transgenics, especially when different zones within the lung were compared (Fig. 5). Alveolar air space occupied a larger percentage of the lung parenchyma in transgenic mice than in non-transgenic mice (Fig. 6). Collagen abundance was estimated in histological sections as picro-Sirius red positive material by previously-published methods. In intrapulmonary conducting airways, collagen was 4.8% of the wall in transgenics and 4.5% of the wall in non-transgenic mice. Since airways represented a smaller percentage of the lung in transgenics, the volume of interstitial collagen associated with airway wall was significantly less. In intrapulmonary blood vessels, collagen was 8.9% of the wall in transgenics and 0.7% of the wall in non-transgenics. Since blood vessels were a smaller percentage of the lungs in transgenics, the volume of collagen associated with the walls of blood vessels was five times greater. In the lung parenchyma, collagen was 51.5% of the tissue volume in transgenics and 21.2% in non-transgenics. Since parenchyma was a larger percentage of lung volume in transgenics, but the parenchymal tissue was a smaller percent of the volume, the volume of collagen associated with parenchymal tissue was only slightly greater. We conclude that overexpression of TGF-α during lung maturation alters many aspects of lung development, including branching morphogenesis of the airways and vessels and alveolarization in the parenchyma. Further, the increases in visible collagen previously associated with pulmonary fibrosis due to the overexpression of TGF-α are a result of actual increases in amounts of collagen and in a redistribution of collagen within compartments which results from morphogenetic changes. These morphogenetic changes vary by lung compartment. Supported by HL20748, ES06700 and the Cystic Fibrosis Foundation.

Sign in / Sign up

Export Citation Format

Share Document