Biomedical subjects

Brigitte Lankat-Buttgereit

Publications and source records attributed to Brigitte Lankat-Buttgereit.

5 recordsLinked to original sources

PubMed2005

Effects of the tyrosine kinase inhibitor imatinib on neuroendocrine tumor cell growth.

AIM: We investigated the effects of the tyrosine kinase inhibitor imatinib (Gleevec) on neuroendocrine tumor cells. METHODS: Neuroendocrine tumor cells were incubated without and with imatinib. The effects on growth were examined by methylthiazoletetrazolium (MTT) assay. The c-Kit expression in human endocrine tumor tissue and cell lines was determined by immunohistochemistry and Western blot analysis, respectively. Cytotoxicity assay was performed by fluorescence-activated cell sorting. The telomerase activity was determined using the telomeric repeat amplification protocol. RESULTS: 28% of the insulinomas, 100% of the gastrinomas, and 38% of the carcinoids expressed c-Kit. Imatinib at concentrations >5 microM inhibited cell proliferation and induced apoptosis in both c-Kit-positive and c-Kit-negative cell lines. The PI-3K inhibitor wortmannin did not enhance the effects of imatinib. Imatinib did not sensitize endocrine tumor cells to doxorubicin and 5-fluorouracil. Imatinib inhibited the telomerase activity. CONCLUSION: Imatinib inhibits neuroendocrine tumor cell growth independently of c-Kit by inhibition of other tyrosine kinases or through tyrosine kinase independent pathways.

Apoptosis↗

PubMed2004

Programmed cell death protein 4 (PDCD4) acts as a tumor suppressor in neuroendocrine tumor cells.

PDCD4 is a new tumor suppressor gene. In the current study, we show that overexpression of PDCD4 in carcinoid cells results in inhibition of cell proliferation. This is most likely caused by a PDCD4-induced downregulation of carbonic anhydrase type II which catalyzes the production of bicarbonate, a fundamental substrate for many cellular pathways.

Apoptosis↗

PubMed2003

Functional cysteine-less subunits of the transporter associated with antigen processing (TAP1 and TAP2) by de novo gene assembly.

Within the adaptive immune system the transporter associated with antigen processing (TAP) plays a pivotal role in loading of peptides onto major histocompatibility (MHC) class I molecules. As a central tool to investigate the structure and function of the TAP complex, we created cysteine-less human TAP subunits by de novo gene synthesis, replacing all 19 cysteines in TAP1 and TAP2. After expression in TAP-deficient human fibroblasts, cysteine-less TAP1 and TAP2 are functional with respect to adenosine triphosphate (ATP)-dependent peptide transport and inhibition by ICP47 from herpes simplex virus. Cysteine-less TAP1 and TAP2 restore maturation and intracellular trafficking of MHC class I molecules to the cell surface.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Programmed cell death protein 4 (pdcd4): a novel target for antineoplastic therapy?

Pdcd4 is a novel gene first identified as a differentially expressed protein during apoptosis. In the meantime not only the impact of Pdcd4 in programmed cell death but also an implication in transformation suppression by inhibition of protein translation is discussed. These features implicate a potential value of Pdcd4 as a molecular target in cancer therapy. This review summarizes the current knowledge about expression, structure and function of Pdcd4.

Animals↗

PubMed2002

The transporter associated with antigen processing: function and implications in human diseases.

The adaptive immune systems have evolved to protect the organism against pathogens encountering the host. Extracellular occurring viruses or bacteria are mainly bound by antibodies from the humoral branch of the immune response, whereas infected or malignant cells are identified and eliminated by the cellular immune system. To enable the recognition, proteins are cleaved into peptides in the cytosol and are presented on the cell surface by class I molecules of the major histocompatibility complex (MHC). The transport of the antigenic peptides into the lumen of the endoplasmic reticulum (ER) and loading onto the MHC class I molecules is an essential process for the presentation to cytotoxic T lymphocytes. The delivery of these peptides is performed by the transporter associated with antigen processing (TAP). TAP is a heterodimer of TAP1 and TAP2, each subunit containing transmembrane domains and an ATP-binding motif. Sequence homology analysis revealed that TAP belongs to the superfamily of ATP-binding cassette transporters. Loss of TAP function leads to a loss of cell surface expression of MHC class I molecules. This may be a strategy for tumors and virus-infected cells to escape immune surveillance. Structure and function of the TAP complex as well as the implications of loss or downregulation of TAP is the topic of this review.

ATP Binding Cassette Transporter, Subfamily B, Mem↗