Integration of murine leukemia virus DNA depends on mitosis.

Roe, Taiyun; Reynolds, Thomas; Yu, Guanhua; Brown, Patrick O.

doi:10.1002/j.1460-2075.1993.tb05858.x

Cited by 875 publications

(661 citation statements)

References 58 publications

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“…In our particular case, it is important to remember that MMTV, as most retroviruses, can insert only in division competent cells. 26,27 Second, these cells could be committed not only to a secretory phenotype, but also to the secretion of a particular protein. Robinson et al 28 showed that the different pattern of expression of WAP and ␤-casein during mammary development suggests the possibility of different secretory cells committed to express either one of these proteins.…”

Section: High Expression At the Wap Promoter In Mmtv-induced Tumors Gmentioning

confidence: 99%

Impairment of mammary lobular development induced by expression of TGF?1 under the control of WAP promoter does not suppress tumorigenesis in MMTV-infected transgenic mice

et al. 2001

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It has previously been shown that transgenic female mice expressing TGF␤1 under control of regulatory elements of the whey-acidic protein (WAP) gene were unable to lactate. This was due to the increased apoptosis of the cells committed to the lobular-lactogenic phenotype. Our goal was to determine whether the expression of WAP-TGF␤1 transgene could inhibit MMTV (mouse mammary tumor virus) tumorigenic activity in the mammary gland. It is well known that the infection with this virus produces focal hyperplastic secretory nodules (HANs) and, some variants can also induce ductal pregnancy-dependent lesions (plaques). In either case, MMTV infection leads ultimately to the appearance of malignant mammary tumors. The results shown herein demonstrate that TGF␤1 expression in the secretory mammary epithelium does not suppress mammary tumorigenesis in MMTV infected mice. Although MMTV infected WAP-TGF␤1 transgenic females displayed a strong impairment of lobule-alveolar development, carcinogenesis induced by any of the four MMTV variants used herein proceeded unabated. WAP-TGF␤1 tumors that showed a strong expression at the WAP promoter, appeared later and grew more slowly than their wild-type counterparts. Transgenic females also had a lower incidence of HANs and plaques. Our study suggests that the epithelial target cells for tumorigenic mutations are probably progenitor cells that are not susceptible to the apoptotic effect of TGF␤1. Alternatively, their daughters cells that display the secretory phenotype and could be more involved in the formation of premalignant lesions continue to die due to the expression of the transgene. © 2001 Wiley-Liss, Inc. Key words: mammary tumor; MMTV; TGF␤1; stem cellsTransforming growth factor-␤1 is a member of a large superfamily of polypeptides and seems to affect many key events in normal growth and differentiation. 1,2 There is good evidence that members of the TGF␤1 gene family may indeed contribute essential signals for the development and secretory maturation of the mammary epithelium. An approach to TGF␤ function and mammary gland development has been the use of transgenic mice. TGF␤1 has been targeted to the mammary epithelium from different transcriptional promoters in two transgenic mouse models. In one, the mouse mammary tumor virus-long terminal repeat (MMTV-LTR) was used to promote expression of TGF␤1 in mammary epithelium. 3 In this biological model, a transient but distinct inhibition of mammary ductal extension and side branching was observed between 3 and 6 weeks of age; however subsequent development during pregnancy and lactation proceeded apparently unperturbed. In the second transgenic mouse model, TGF␤1 was expressed under the control of the whey acidic protein (WAP) promoter. This promoter is mammary epithelium-specific and most active during late pregnancy and lactation. In this model no inhibition of mammary ductal growth at puberty was observed. 4 With the onset of pregnancy, lobule-alveolar growth and development were impaired to the extent that lactation was...

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Section: High Expression At the Wap Promoter In Mmtv-induced Tumors Gmentioning

confidence: 99%

Impairment of mammary lobular development induced by expression of TGF?1 under the control of WAP promoter does not suppress tumorigenesis in MMTV-infected transgenic mice

et al. 2001

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“…One of these strategies is to anchor pDNA to the chromatin during cell division, so that the nanoparticles efficiently are enclosed in the nuclei of the daughter cells. This strategy is in fact used by some retroviruses and some latent DNA viruses taking advantage of mitosis [10][11][12][13]. Binding of DNA or DNA nanoparticles to chromatin could both enhance the nuclear inclusion and increase the probability that pDNA is passed on during subsequent cell divisions.…”

Section: Introductionmentioning

confidence: 99%

Cell division responsive peptides for optimized plasmid DNA delivery: The mitotic window of opportunity?

Remaut

Symens

Lucas

et al. 2014

Journal of Controlled Release

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The delivery of plasmid DNA remains hard to achieve, especially due to the presence of the nuclear membrane barrier. During cell division, however, the nuclear membrane is temporarily disassembled. We evaluated two different strategies to optimize plasmid DNA delivery in dividing cells: 1) phosphorylation responsive peptides that release plasmid DNA preferentially during mitosis and 2) chromatin targeting peptides to anchor plasmid DNA in newly formed nuclei upon cell division. Peptide/DNA particles alone were not efficient in penetrating cells. Upon co-delivery with lipid-based carriers, however, transfection efficiency drastically improved when compared to controls. For the phosphorylation responsive peptides, the presence of the phosphorylation sequence slightly increased transfection efficiency. For the chromatin targeting peptides, however, the chromatin targeting sequence did not seem to be the main reason for the improvement of transfection efficiency when applied in living cells. In conclusion, the pre-condensation of plasmid DNA with peptides improves lipid based delivery, but the nature of the peptides (cell responsive or not) does not seem to be the main reason for the improvement. It seems that the nuclear entry of foreign plasmid DNA is still under tight control, even during the mitotic window of opportunity.

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“…10,11 A major limitation of the currently available retroviral vectors is their requirement for target cells to transit the cell cycle in order for proviral integration to occur. 12,13 Mobilised peripheral blood stem cells are generally quiescent and are thus intrinsically refractory to transduction by such vectors. 14 Attempts to improve transduction efficiency by using cocktails of haemopoietic growth to induce entry into the cell cycle resulted in only transient marking of cells in vivo, suggesting that retroviral integration had occurred in committed progenitors rather than stem cells.…”

Section: Introductionmentioning

confidence: 99%

Feasibility of multidrug resistance (MDR-1) gene transfer in patients undergoing high-dose therapy and peripheral blood stem cell transplantation for lymphoma

et al. 1998

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We have performed a pilot study of MDR-1 gene transfer chain reaction (PCR) for vector-derived MDR-1 cDNA in patients receiving CD34-selected peripheral blood stem sequence in all cases. Analysis of peripheral blood and cell (PBSC) transplant for lymphoma. To ensure minimum bone marrow cells after transplant has, however, shown engraftment thresholds and facilitate CD34 purification, no evidence of in vivo gene transfer with a follow-up of 12, mobilisation of Ͼ2 × 10 6 CD34 cells/kg was a condition for 15 and 18 months. The effect of MDR-1 substrate drugs recruitment. Of 11 patients counselled for study entry, onlyhas not yet been tested as all patients remain in clinical five achieved this target in a single apheresis. In three conand radiological remission of their lymphoma. These senting patients, purified CD34 cells were exposed to results confirm the difficulty of achieving in vivo gene trans-A12M1 MDR-1 retroviral supernatant for 6 h, cryoprefer in human haemopoietic cells and indicate major logisserved then thawed and readministered following ablative tical constraints in PBSC mobilisation in patients with chemotherapy. No delay in engraftment was observed, relapsed and resistant disease in whom initial studies are although one patient received additional back-up cells.appropriate. Gene transfer was demonstrated by polymerase

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Integration of murine leukemia virus DNA depends on mitosis.

Cited by 875 publications

References 58 publications

Impairment of mammary lobular development induced by expression of TGF?1 under the control of WAP promoter does not suppress tumorigenesis in MMTV-infected transgenic mice

Impairment of mammary lobular development induced by expression of TGF?1 under the control of WAP promoter does not suppress tumorigenesis in MMTV-infected transgenic mice

Cell division responsive peptides for optimized plasmid DNA delivery: The mitotic window of opportunity?

Feasibility of multidrug resistance (MDR-1) gene transfer in patients undergoing high-dose therapy and peripheral blood stem cell transplantation for lymphoma

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