Biomedical subjects

Silke Kuphal

Publications and source records attributed to Silke Kuphal.

4 recordsLinked to original sources

PubMed2005

Integrin signaling in malignant melanoma.

Cell adhesion and migration are essential for embryonic development, tissue regeneration, but also for tumor development. The physical link between the extracellular matrix (ECM) and the actin cytoskeleton is mainly mediated by receptors of the integrin family. Through signals transduced upon integrin ligation to ECM proteins, this family of proteins plays key roles in regulating tumor growth and metastasis as well as tumor angiogenesis. During melanoma development, changes in integrin expression, intracellular control of integrin functions and signals perceived from integrin ligand binding impact upon the ability of tumor cells to interact with their environment and enable melanoma cells to convert from a sessile, stationary to a migratory and invasive phenotype. Antagonists of several integrins are now under evaluation in clinical trials to determine their potential as therapeutics for malignant melanoma and other kinds of cancer.

Cell Adhesion↗

PubMed2005

Snail-regulated genes in malignant melanoma.

The demonstration that zinc-finger transcriptional repressors can control E-cadherin expression in epithelial cells has provided a new avenue of research in the field of epithelial-mesenchymal transition (EMT). One of these zinc-finger molecules is the transcription factor Snail, which controls gastrulation and neural crest EMT in different species. Additionally, Snail is involved in the development of malignant melanoma where a dramatic change in E-cadherin expression is an important early step for melanoma progression. For this study, a human cancer cDNA array was used which includes genes involved in cancer development and progression. Using the array we compared the gene expression pattern of the melanoma cell line Mel Im with a Mel Im cell clone stable transfected with antisense (as) SNAIL cDNA. We validated the significant differences of the expression of genes on mRNA level. Primarily, we observed changes in the expression of genes involved in EMT. Quantitative real-time polymerase chain reaction showed a down-regulation of MMP-2, EMMPRIN, SPARC, TIMP-1, t-PA, RhoA and Notch4 expression and a re-induction of E-cadherin expression in the as Snail cell clones. Furthermore, we measured the expression of integrin beta3, NM23b and RhoB. Additionally, we investigated whether the selected genes are influenced only through Snail or if E-cadherin can influence the expression of these genes. In summary, all examined genes which are influenced through Snail have a regulatory function in EMT processes as does Snail itself. The Snail target gene E-cadherin has no regulatory function with respect to the selected genes.

Cadherins↗

PubMed2004

Functional role of MIA in melanocytes and early development of melanoma.

The protein MIA (melanoma inhibitory activity) is highly expressed in malignant melanomas but not in melanocytes. Furthermore, expression of MIA correlates with tumor progression in vivo. Here, MIA-dependent changes of gene expression after long-term inhibition of MIA expression in the human melanoma cell line HMB2 were investigated. Primarily, we observed characteristic changes in cell morphology, and also found re-established cell-cell contacts in MIA-deficient cell clones grown in monolayer culture. Real-time reverse transcription-polymerase chain reaction (RT-PCR) showed a downregulation of N-cadherin expression and a reinduction of E-cadherin expression in the MIA-deficient cell clones. Further, both cancer cDNA array and protein arrays verified a marked downregulation of several other melanoma-associated genes (e.g. membrane-type 1 matrix metalloproteinase tissue-type plasminogen activator integrin beta3, secreted protein acidic and rich in cysteins and fibronectin) in the MIA-deficient melanoma cells, confirmed by real-time RT-PCR and Western blotting. As all these molecules are associated with migration, the effect of MIA on migration of human primary melanocytes was analysed. In the presence of MIA, we observed enhanced migratory ability of melanocytic cells, induction of melanoma-associated genes as well as inhibition of apoptosis due to anoikis. These results suggest that expression of MIA promotes melanoma progression by inducing further melanoma-associated genes.

Cell Adhesion Molecules↗

PubMed2002

A single flavoprotein, AppA, integrates both redox and light signals in Rhodobacter sphaeroides.

Anoxygenic photosynthetic proteobacteria exhibit various light responses, including changing levels of expression of photosynthesis genes. However, the underlying mechanisms are largely unknown. We show that expression of the puf and puc operons encoding structural proteins of the photosynthetic complexes is strongly repressed by blue light under semi-aerobic growth in Rhodobacter sphaeroides but not in the related species Rhodobacter capsulatus. At very low oxygen tension, puf and puc expression is independent of blue light in both species. Photosynthetic electron transport does not mediate the blue light repression, implying the existence of specific photoreceptors. Here, we show that the flavoprotein AppA is likely to act as the photoreceptor for blue light-dependent repression during continuous illumination. The FAD cofactor of AppA is essential for the blue light-dependent sensory transduction of this response. AppA, which is present in R. sphaeroides but not in R. capsulatus, is known to participate in the redox-dependent control of photosynthesis gene expression. Thus, AppA is the first example of a protein with dual sensing capabilities that integrates both redox and light signals.

Bacterial Proteins↗