| 1. |
|
|
| 2. |
- Gal, Annamaria, et al.
(författare)
-
Sustained TGF beta exposure suppresses Smad and non-Smad signalling in mammary epithelial cells, leading to EMT and inhibition of growth arrest and apoptosis
- 2008
-
Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 27:9, s. 1218-1230
-
Tidskriftsartikel (refereegranskat)abstract
- To better understand the dual, tumour-suppressive and tumour-promoting function of transforming growth factor-beta (TGFbeta), we analysed mammary epithelial NMuMG cells in response to short and long-term TGFbeta exposure. NMuMG cells became proliferation-arrested and apoptotic after exposure to TGFbeta for 2-5 days, whereas surviving cells underwent epithelial-mesenchymal transition (EMT). After chronic TGFbeta exposure (2-3 weeks), however, NMuMG cells became resistant to proliferation arrest and apoptosis, showing sustained EMT instead (TD cells). EMT was fully reversed by a pharmacologic TGFbeta-receptor-I kinase inhibitor or withdrawal of TGFbeta for 6-12 days. Interestingly, both cell cycle arresting/proapoptotic (Smads, p38 kinase) and antiapoptotic, proliferation and EMT-promoting signalling pathways (PI3K-PKB/Akt, ERK) were co-suppressed to low, but significant levels. Except for PI3K-Akt, TGFbeta-dependent downregulation of these signalling pathways in transdifferentiated (TD) cells was fully reversed upon TGFbeta withdrawal, together with partial re-induction of proliferation arrest and apoptosis. Co-injection of non-tumorigenic NMuMG cells with tumour-forming CHO cells oversecreting exogenous TGFbeta1 (CHO-TGFbeta1) allowed outgrowth of epithelioid cells in CHO-TGFbeta1 cell-induced tumours. These epithelial islands enhanced CHO-TGFbeta1 tumour cell proliferation, possibly due to chemokines (for example, JE/MCP-1) secreted by NMuMG/TD cells. We conclude that suppression of antiproliferative, proapoptotic TGFbeta signalling in TD cells may permit TGFbeta-dependent proliferation, survival and EMT-enhancing signalling pathways to act at low levels. Thus, TGFbeta may modulate its own signalling to facilitate switching from tumour suppression to tumour progression.
|
|
| 3. |
- Gromov, S P, et al.
(författare)
-
Self-assembly of a (benzothiazolyl)ethenylbenzocrown ether into a sandwich complex and stereoselective [2+2] photocycloaddition
- 2005
-
Ingår i: RUSSIAN CHEMICAL BULLETIN. - : Springer Science and Business Media LLC. - 1066-5285 .- 1573-9171. ; 54:7, s. 1569-79
-
Tidskriftsartikel (refereegranskat)abstract
- In the presence of Ba2+ ions, (benzothiazolyl)ethenylbenzocrown ether forms the stable sandwich complex 2L center dot Ba2+ with an unusual structure, in which the benzothiazole fragments are arranged one above the other. Irradiation of the sandwich complex with visible light induces stereoselective [2+2] cycloaddition giving rise to two "head-to-head" isomers of biscrown-cyclobutane. The addition of dibasic dicarboxylic acids that additionally stabilize the sandwich complex in a favorable conformation affects the isomer ratio of the cyclobutanes formed. The conformational equilibria for the sandwich complex and cyclobutanes were studied by H-1 N MR spectroscopy.
|
|
| 4. |
|
|
| 5. |
|
|
