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001-es BibID:	BIBFORM004656
035-os BibID:	WOS:000088961100053
Első szerző:	Bacsó Zsolt (biofizikus)
Cím:	The DNA of annexin V-binding apoptotic cells is highly fragmented / Bacso, Z., Everson, R. B., Eliason, J. F.
Dátum:	2000
Megjegyzések:	Jurkat leukemia cells induced to undergo apoptosis by treatment with an antibody against the Fas receptor have two annexin V (AV)-binding subpopulations: (a) single-positive cells that bind AV but not propidium iodide (PI); and (b) double-positive cells that bind AV and PI. The single-positive population is thought to represent an early stage of apoptosis. We have examined the relationship between AV binding and a classical characteristic of apoptosis, DNA fragmentation. Time course studies with Jurkat cells treated for 1, 2, or 4 h with anti-Fas indicated that the proportion of AV-binding cells was increased after 2 h. A significant increase in DNA fragmentation was observed only at 4 h as measured by the mean tail moment determined with the alkaline single cell gel electrophoresis (comet) assay. This correlation suggests a temporal relationship between the two parameters, but does not provide direct evidence of what happens in individual cells. We developed a method to measure fluorescent markers of cellular structure or function with a laser scanning cytometer and then perform the comet assay on the same cells. Cells in each AV-binding subpopulation were re-examined before and after electrophoresis. Most AV-/PI- cells had no DNA damage, although a few cells showed a pattern of damage characteristic for apoptosis. Double-positive cells all had damaged DNA; approximately half had the apoptotic pattern, and the rest had a pattern typical for necrosis. Nearly all of the single-positive cells had damaged DNA with the apoptotic pattern. Both AV-positive populations contained cells with little or no detectable DNA after electrophoresis, indicating that the DNA was highly fragmented. These results indicate that AV binding is an excellent marker for apoptotic cells, but that these cells already have fragmented DNA.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Annexin V Antibodies Antibodies, Monoclonal Antigens, CD95 Apoptosis Cell Membrane Cells Comet Assay cytology Dna DNA Damage DNA Fragmentation DNA, Neoplasm Dyes Flow Cytometry Human immunology Jurkat Cells metabolism Necrosis pharmacology Phosphatidylserines physiology Propidium Support, Non-U.S.Gov't Tumor Cells, Cultured külföldön készült közlemény
Megjelenés:	Cancer research. - 60 : 16 (2000), p. 4623-4628. -
További szerzők:	Everson, Richard B. Eliason, James F.
Internet cím:	elektronikus változat
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001-es BibID:	BIBFORM004879
Első szerző:	Nagy Péter (biofizikus)
Cím:	Decreased accessibility and lack of activation of ErbB2 in JIMT-1, a herceptin-resistant, MUC4-expressing breast cancer cell line / Nagy, P., Friedlander, E., Tanner, M., Kapanen, A. I., Carraway, K. L., Isola, J., Jovin, T. M.
Dátum:	2005
ISSN:	0008-5472
Megjegyzések:	Overexpression of erbB2 in breast tumors is associated with poor prognosis and is a target of receptor-oriented cancer therapy. Trastuzumab (Herceptin), a monoclonal antibody against a membrane-proximal epitope in the extracellular region of erbB2, shows a therapeutic effect against a fraction of erbB2-amplified breast tumors. Unfortunately, resistance to Herceptin is common, and its cause is as yet unclear. Here we investigated the properties of erbB2 in a Herceptin-resistant cell line, JIMT-1, established from a breast cancer patient showing erbB2 gene amplification and primary resistance to Herceptin. The expression profile of erbB proteins, Herceptin-induced erbB2 internalization, and down-regulation in JIMT-1 were similar to those in Herceptin-sensitive lines. However, the mean number of Herceptin Mab binding sites in JIMT-1 was 1/5 that of the expressed erbB2 molecules, although 5% to 10% of the cells showed a approximately 10-fold higher Herceptin binding than the main population. Herceptin Fab and Mab 2C4, an antibody binding to an epitope in the ectodomain further removed from the membrane, bound more efficiently to JIMT-1 cells than Herceptin Mab, implying that erbB2 was partly masked. The expression of MUC4, a membrane-associated mucin that according to reports contributes to the masking of membrane proteins, was higher in JIMT-1 than in Herceptin-sensitive lines, and its level was inversely correlated with the Herceptin binding capacity of single cells. Knockdown of MUC4 expression by RNA interference increased the binding of Herceptin. Western blotting showed a low level of proteolytic processing, shedding, and tyrosine phosphorylation of erbB2 in JIMT-1. The latter finding may explain its Herceptin-resistant phenotype characterizing both the low and high Herceptin binding subpopulations. We conclude that masking of erbB2 in JIMT-1 leads to diminished Herceptin binding and isolation of erbB2 from its normal interaction and activation partners.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Antibodies Antibodies,Monoclonal Antineoplastic Agents Binding Sites biosynthesis Breast Neoplasms Cell Line Cell Line,Tumor Cells chemistry Down-Regulation Drug Resistance,Neoplasm drug therapy Enzyme Activation enzymology Epitopes Gene Amplification Humans immunology Membrane Proteins metabolism Metalloproteases Mucins pharmacology Phenotype Phosphorylation Proteins Receptor,erbB-2 Research Support therapy Tyrosine
Megjelenés:	Cancer Research. - 65 : 2 (2005), p. 473-482. -
További szerzők:	Friedländer Elza (1980-) (biofizikus) Tanner, Minna Kapanen, Anita I. Carraway, Kermit L. Isola, Jorma Jovin, Thomas M.
Internet cím:	elektronikus változat
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