Biomedical subjects

Guido Jenster

Publications and source records attributed to Guido Jenster.

22 records · Page 2Linked to original sources

PubMed2004

The TRPS1 transcription factor: androgenic regulation in prostate cancer and high expression in breast cancer.

TRPS1 mRNA is more highly expressed in androgen-dependent lymph node carcinoma of prostate-fast growing colony (LNCaP-FGC) compared with androgen-independent lymph node carcinoma of prostate-lymph node original (LNCaP-LNO) prostate cancer cell lines. Furthermore, TRPS1 mRNA expression is down-regulated by androgens in LNCaP-FGC cells, a process mediated by the androgen receptor (AR). Here, we present TRPS1 protein expression in human prostate cancer material derived from a panel of six androgen-dependent and eight androgen-independent human prostate cancer xenografts. TRPS1 protein is expressed in all androgen-dependent xenografts, which also express AR and prostate-specific antigen (PSA). Androgen withdrawal by castration resulted in an increase in TRPS1 protein in two androgen-dependent xenografts, indicating relieved repression by action of AR. TRPS1 protein is expressed in four androgen-independent xenografts and is low or absent in the other four androgen-independent xenografts. Androgen withdrawal by castration demonstrates that TRPS1 protein levels remain the same in 1 androgen-independent xenograft, most likely due to the lack of AR expression. These data show that TRPS1 protein expression is regulated by androgens via the AR in human prostate cancer xenografts. Analysis of TRPS1 mRNA expression in normal and tumour tissue of the prostate and 18 other human tissues, showed that TRPS1 had the highest mRNA expression levels in normal and tumour tissues of breast. In addition, high TRPS1 mRNA and protein expression levels were observed in four out of five human breast cancer cell lines. In conclusion, TRPS1 protein expression is down-regulated by androgens in human prostate cancer, and analysis of TRPS1 mRNA expression levels in several human tissues showed that the highest levels were observed in normal and tumour breast tissue.

Animals↗

PubMed2003

Venn Mapping: clustering of heterologous microarray data based on the number of co-occurring differentially expressed genes.

MOTIVATION: To evaluate microarray data, clustering is widely used to group biological samples or genes. However, problems arise when comparing heterologous databases. As the clustering algorithm searches for similarities between experiments, it will most likely first separate the data sets, masking relationships that exist between samples from different databases. RESULTS: We developed a program, Venn Mapper, to calculate the statistical significance of the number of co-occurring differentially expressed genes in any of the two experiments. For proof of principle, we analysed a heterologous data set of 170 microarrays including breast and prostate cancer microarray analyses. Significant overlap was found in an unsupervised analysis between metastasized prostate cancer and metastasized breast cancer and BRCA mutated breast cancer. A comparison between single microarray data and the averaged breast and prostate data sets was also evaluated. This analysis suggests that genes expressed higher in stromal cells are also implicated in metastatic prostate cancer and BRCA mutated breast cancer. The Venn Mapper program identifies overlaps between samples from heterologous data sets and directly extracts the genes responsible for the overlap. From this information novel biological hypotheses may be addressed. AVAILABILITY: Venn Mapper is freely available on http://www.erasmusmc.nl/gatcplatform. SUPPLEMENTARY INFORMATION: http://www.erasmusmc.nl/gatcplatform/vennmapper.html.

Algorithms↗

PubMed2003

AKT-independent protection of prostate cancer cells from apoptosis mediated through complex formation between the androgen receptor and FKHR.

Recent studies suggested that the protection of cell apoptosis by AKT involves phosphorylation and inhibition of FKHR and related FOXO forkhead transcription factors and that androgens provide an AKT-independent cell survival signal in prostate cancer cells. Here, we report receptor-dependent repression of FKHR function by androgens in prostate cancer cells. Transcriptional analysis demonstrated that activation of the androgen receptor caused an inhibition of both wild-type FKHR and a mutant in which all three known AKT sites were mutated to alanines, showing that the repression is AKT independent. In vivo and in vitro coprecipitation studies demonstrated that the repression is mediated through protein-protein interaction between FKHR and the androgen receptor. Mapping analysis localized the interacting domains to the carboxyl terminus between amino acids 350 and 655 of FKHR and to the amino-terminal A/B region and the ligand binding domain of the receptor. Further analysis demonstrated that the activated androgen receptor blocked FKHR's DNA binding activity and impaired its ability to induce Fas ligand expression and prostate cancer cell apoptosis and cell cycle arrest. These studies identify a new mechanism for androgen-mediated prostate cancer cell survival that appears to be independent of the activity of the receptor on androgen response element-mediated transcription and establish FKHR and related FOXO forkhead proteins as important nuclear targets for both AKT-dependent and -independent survival signals in prostate cancer cells.

Apoptosis↗

PubMed2003

Mining microarray datasets aided by knowledge stored in literature.

DNA microarray technology produces large amounts of data. For data mining of these datasets, background information on genes can be helpful. Unfortunately most information is stored in free text. Here, we present an approach to use this information for DNA microarray data mining.

Databases, Genetic↗