Mouse Model Systems to Study Multistep Tumorigenesis

Berns, Anton; Lugt, N van der; Alkema, Manon; Lohuizen, Maarten van; Domen, Jos; Acton, D; Allen, Jeffrey D.; Laird, Peter W.; Jonkers, Jos

doi:10.1101/sqb.1994.059.01.049

Cited by 24 publications

(29 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Induction of Gfi-1 by IL-4 increases Th2 cell expansion by promoting proliferation and preventing apoptosis (10). Gfi-1 cooperates with the cell-cycle regulators PIM-1 and cMyc (6,7,40). The E2F family of transcription factors also plays a critical role in cell-cycle progression through its ability to regulate the expression of target genes, including cyclins and cyclin-dependent kinases (41).…”

Section: Discussionmentioning

confidence: 99%

Targets of the transcriptional repressor oncoprotein Gfi-1

Duan

Horwitz

2003

Proc. Natl. Acad. Sci. U.S.A.

103

View full text Add to dashboard Cite

The undersigned authors note the following: "We wish to bring to your attention an issue regarding our PNAS publication referenced above. Although we cite our earlier PNAS publication (see ref. Figs. 2 and 3 display the UWHBs for Hb β-subunit (pdb.1bz0, chain B) and human cellular prion protein (pdb.1qm0) (12)(13)(14). Within the natural interactive context of the Hb subunit, the UWHBs signal crucial binding regions (24): UWHBs (90, 94), (90, 95) are associated with the β-FG corner involved in the quaternary α1β2 interface; UWHB (5, 9) is adjacent to Glu-6 which in sickle cell anemia mutates to Val-6 and is located at the Val-6-(Phe-85, Leu-88) interface in the deoxyHbS fiber."The following text in the section titled 'Toward a Structural Diagnosis' on page 6449 of our text is similar to the text beginning in the last paragraph on page 2392 in ref. 23:The distribution of proteins according to their average extent of hydrogen bond wrapping and their spatial concentration of structural defects is shown in Fig. 5 (see also ref. 23). The sample of 2,811 PDB proteins is large enough to define a reliable abundance distribution with an inflection point at ρ = 6.20. The integration of the distribution over a ρ-interval gives the fraction of proteins whose ρ lies within that range. Of the 2,811 proteins examined, 2,572 have ρ > 6.20, and none of them is known to yield amyloid aggregation under physiological conditions entailing partial retention of structure. Strikingly, relatively few disease-related amyloidogenic proteins are known in the sparsely populated, underwrapped 3.5 < ρ < 6.20 range, with the cellular prion proteins located at the extreme of the spectrum (3.53 < ρ < 3.72)....The range of H-bond wrapping 3.5 < ρ < 4.6 of 20 sampled PDB membrane proteins has been included in Fig. 5 for comparison. As expected, such proteins do not have the stringent H-bond packing requirements of soluble proteins for their H bonds at the lipid interface. Thus, this comparison becomes suggestive in terms of elucidating the driving factor for aggregation in soluble proteins: Although the UWHB constitutes a structural defect in a soluble protein because of its vulnerability to water attack, it is not a structural defect in a membrane protein. The exposure of the polar amide and carbonyl of the unbound state to a nonpolar phase is thermodynamically unfavorable (22). The virtually identical ρ value for human prion and outer-membrane protein A (Fig. 5) is revealing in this regard.Furthermore, all known amyloidogenic proteins that occur naturally in complexed form have sufficient H-bond wrapping within their respective complexes (ρ value near 6.2). Their amyloidogenic propensity appears only under conditions in which the protein is dissociated from the complex (compare Fig. 5). This finding is corroborated by the following computation. If an intramolecular hydrogen bond is underwrapped within the isolated protein molecule but located at an interface upon complexation, then to determine its extent of wrapping within the complex, we take ...

show abstract

Section: Discussionmentioning

confidence: 99%

Targets of the transcriptional repressor oncoprotein Gfi-1

Duan

Horwitz

2003

Proc. Natl. Acad. Sci. U.S.A.

103

View full text Add to dashboard Cite

show abstract

“…Unlike EmMyc B cells, transgenic T cells do normally not express the c-Myc transgene (Langdon et al, 1986;Alexander et al, 1987), whereas upregulation of Myc, through either direct or indirect mechanisms, is invariably seen in MuLV-induced lymphomas (Berns et al, 1994). In addition, it has been shown that EmMyc B cell lymphomas, both the spontaneous as well as the MuLV-induced tumors, have lost the endogenous c-Myc mRNA and only express the transgenic copy (Adams et al, 1985;van Lohuizen et al, 1991).…”

Section: Resultsmentioning

confidence: 99%

Proviral activation of the tumor suppressor E2a contributes to T cell lymphomagenesis in EμMyc transgenic mice

2002

View full text Add to dashboard Cite

The basic helix -loop -helix factor E2A plays an important role in the development of B and T lymphocytes. In addition, E2a has been implicated as a gene with tumor suppressor activity, since mice deficient for E2a succumb to T cell lymphomas. We have performed retroviral tagging in EmMyc transgenic mice to identify genes that contribute to lymphomagenesis. The EmMyc transgenic mouse is a well-established model of a common translocation in human B cell lymphomas. Analyses of the proviral insertion sites in the MuLVinduced lymphomas revealed that a number of T cell lymphomas carried proviral insertions in the promoter region of E2a. These proviral insertions yield hybrid viral-E2a mRNAs resulting in a marked rise in E2A protein levels. The proviral insertions in E2a were predominantly of clonal origin indicating that E2a insertions are early events in these T cell lymphomas. The primary oncogenic effect of E2A is likely to be associated with enhancement of transcription of the cMyc transgene via binding to the regulatory immunoglobulin enhancers. The results herein thus provide the first evidence that in a specific setting E2A overexpression can contribute to T-lymphomagenesis. This implies that E2a contains oncogenic features in addition to the previously described tumor suppressive properties.

show abstract

“…Se han producido, por ejemplo, ratones propensos a desarrollar tumores, como el transgénico que p53 (12). La detección de eventos tóxicos se mejora introduciendo genes que se activan en presencia de un agente tóxico.…”

Section: Uso De Los Modelos De Ratones Transgénicosunclassified

Ética De La Investigación en Modelos Animales De Enfermedades Humanas

Yunta

2007

Acta bioeth.

View full text Add to dashboard Cite

Resumen la medicina en seres humanos. Entre las posturas extremas de condenar toda investigación con animales considerándola irrelevante y la de exagerar y promocionar el importante papel de la investigación con animales como modelo para enfermedades humanas, se adopta la postura intermedia de considerar el uso de animales en investigación como necesario en el estado actual de la ciencia para ajustarse al imperativo moral de curar y prevenir enfermedades humanas, pero buscando formas de reemplazar y reducir el número de animales y de disminuir su sufrimiento.Palabras clave: bioética, modelo animal, dolor y sustrato moral en los animales ETHICS OF RESEARCH WITH ANIMAL MODELS FOR HUMAN DISEASESAbstract: This paper argues about the ethical implications of using animals as models for human medicine development.considering it irrelevant, and that of exaggerating and promoting research with animals as models for human diseases.imperative of curing and preventing human diseases, but methods for replacing and reducing the number of animals as well as diminishing their suffering must be sought. Key words: bioethics, animal model, pain and moral status in animals ÉTICA DA PESQUISA EM MODELOS ANIMAIS DE ENFERMIDADES HUMANASResumo em sereres humanos. Entre as posturas extremas, uma é a de condenar todas as pesquisas com animais, considerando-a irrelevante e a outra postura, é a de exagerar e promover o importante papel da pesquisa com animais como modelo para enfermidades humanas. Adota-se uma postura intermediária de considerarar o uso de animais em pesquisa, como necessária para o estado atual da ciência para se ajustarao imperativo moral de curar e prevenir enfermidades humanas, porém buscando formas de substituir e reduzir o número de animais e de diminuir seu sofrimento.Palavras chave: Bioética, modelo animal, dor e substrato moral nos animais * Doctor en Biología Celular y Molecular, Master en Teología, Especialidad

show abstract

Mouse Model Systems to Study Multistep Tumorigenesis

Cited by 24 publications

References 0 publications

Targets of the transcriptional repressor oncoprotein Gfi-1

Targets of the transcriptional repressor oncoprotein Gfi-1

Proviral activation of the tumor suppressor E2a contributes to T cell lymphomagenesis in EμMyc transgenic mice

Ética De La Investigación en Modelos Animales De Enfermedades Humanas

Contact Info

Product

Resources

About