Biomedical subjects

A Ullrich

Publications and source records attributed to A Ullrich.

417 records · Page 24Linked to original sources

PubMedDate not supplied

[Gene expression profiles of protein kinases and phosphatases obtained by hybridization with cDNA arrays: molecular portrait of human prostate carcinoma].

Hybridization with cDNA arrays was used to obtain expression profiles of 263 protein-tyrosine kinase (PTK), protein-tyrosine phosphatase (PTP), dual-specific phosphatase (DuSP), and other genes for the normal prostate tissue, primary prostate carcinomas (PC) of 84 patients, 7 xenografts, and 5 carcinoma cell lines. Analysis of 96 profiles revealed eight clusters of genes coexpressed in PC (coefficient of correlation r > 0.7). According to the known functions of their genes, the clusters were designated as proliferating-cell (CDC42, TOP2A, FGFR3, MYC, etc.), neoangiogenesis and blood-cell (LCK, VAV1, KDR, VEGF, MMP9, SYK, PTPRS, and FLT4), invasion-1 and invasion-2 (ADAM17, TRPM2, DUSP6, VIM, CAV1, CAV2, JAK1, PTPNS1, FYN, and PDGFB), HER2, and PSA/PSM/HER3. Basing on expression profiles of 66 genes, a molecular classification of PC was constructed and allowed discrimination between PC and cell lines or xenografts at 98.9% probability. The results suggested that, along with PSA, PSM (FOLH1), kallikrein-2, and a-2-macroglobulin, cell signaling genes EGFR, HER2, HER3, TOP2, KRT8, KRT18, VEGF, CD44, VIM, CAV1, and CAV2 may serve as diagnostic and prognostic markers in PC. The HER2, VEGF, and CD44 genes and the MMP and ADAM families were assumed to be promising targets for inhibitors of PC cell proliferation and metastasis.

Gene Expression Regulation, Neoplastic↗

PubMedDate not supplied

The human EGF receptor gene: structure of the 110 kb locus and identification of sequences regulating its transcription.

The human epidermal growth factor receptor (EGFR) proto-oncogene is shown to span 110 kb of DNA divided into 26 exons. Analysis of sequences surrounding exon 1 reveals a highly CG rich region which promotes transcription. The activity of the EGF receptor promoter can be modulated by E1A protein and receptor RNA levels increased by stimulation with phorbol ester or fetal calf serum. Promoter activity is assayed by linkage to the chloramphenicol acetyl transferase gene and transfection in three cell lines, with quantitation of plasmid DNA uptake by isolation of a Hirt supernatent from each transfection. Deletion analysis of the CG rich promoter region of the gene and construction of chimeric EGFR/SV40 promoters are used to demonstrate positive transcription elements located both within exon 1 and 5' to the start of transcription. Negative regulation of transcription by sequences within a -140 to +80 region is suggested. Cotransfection experiments suggest a requirement for the interaction of DNA binding protein Sp1 for maximal activity. Finally, derepression of a positive regulatory sequence located in exon 1 during cotransfection experiments is shown. Results are discussed in reference to the multilevel regulation of EGF receptor expression.

Amino Acid Sequence↗

PubMedDate not supplied

Coexpression of epidermal growth factor receptor and TGF-alpha and survival in upper aerodigestive tract cancer.

In order to find a prognostic marker for the course of disease in head and neck cancer we hypothesized that patients with rapid disease progress would produce increased levels of transforming growth factor alpha (TGF-alpha) and its cell surface receptor, epidermal growth factor receptor (EGFR). Using molecular biological techniques, we examined the incidence of TGF-alpha and EGFR overexpression in 43 patients with tumors of the head and neck. The expression data was correlated with the course of disease in a 4 year follow-up. The tumors were classified into four groups according to the EGFR status: Group 1, no expression for EGFR (15 samples); group 2, expression level 10 for EGFR (18 samples); group 3, expression level 50 for EGFR (7 samples) and group 4, expression level 100 for EGFR (3 samples). Expression for the TGF-alpha protein was only detected in group 4. There was a significant correlation with EGFR/TGF-alpha overexpression in group 4 and survival compared when with group 3 (p < 0.01) and group 1 (p < 0.05). The mean survival for group 1 to 4 was 27, 23, 34 and 10 months, respectively. The analysis of all patients revealed that the patients who expressed EGFR as well as TGF-alpha had the poorest prognosis. Increased production of TGF-alpha and EGFR in tumors of the head and neck may serve both as a marker for tumor progression and as a target for therapy (e.g. inhibition of the autocrine loop, blockage of TGF-alpha binding).

Adult↗