Biomedical subjects

T Hildebrandt

Publications and source records attributed to T Hildebrandt.

24 records · Page 2Linked to original sources

PubMedDate not supplied

Identification of URIM, a novel gene up-regulated in metastasis.

URIM (Up-Regulated In Metastasis) was identified as a new gene by Differential Display Technique during investigation of the transcriptional pattern of a metastasizing (NMCL-1) and a non-metastasizing (530) human melanoma cell line. The protein is encoded by 206 amino acids with an isoelectric point of 10.4. In addition, URIM displays a putative nuclear localization signal and a putative leucine zipper suggesting that URIM may function as a nuclear protein. Expression of URIM in several normal tissues and tumor cell lines was studied by Northern blotting. Surprisingly, 17 fold increased steady-state mRNA levels for URIM were detected in three cell lines derived from bone marrow micrometastasis of mammary carcinoma and one mammary carcinoma cell line derived from ascites fluid compared to normal epithelial cells from mammary gland and two cell lines derived from primary mammary carcinoma. These findings indicate that expression of URIM might be deregulated in metastases of different types of tumors.

Amino Acid Sequence↗

PubMedDate not supplied

Transcriptional profiling of human mammary carcinoma cell lines reveals PKW, a new tumor-specific gene.

In order to identify genes associated with distinct stages of mammary carcinoma we have investigated the transcriptional profile of normal mammary gland epithelial cells, cell lines derived from primary tumors, from bone marrow micrometastases and from ascites fluid. mRNA's for ribosomal protein L41 and URIM (Up-Regulated In Metastasis) were consistently increased in all cells derived from metastatic lesions. mRNA for human secreted frizzled-related protein (hsFRP) was found to be dramatically down-regulated in all mammary tumor cells compared to non-transformed mammary gland epithelial cells. mRNA for Human Hypoxia Related Factor--2 (HRF-2) and a transcript including the human mitochondrial control region were significantly overexpressed in the cell lines derived from primary tumors and ascites fluid. A new gene, referred to as PKW, was only expressed in one of the primary tumor cell lines, the one derived from a medullary carcinoma. The small and the large transcript which are derived by differential splicing encode potential proteins comprising 95 aa and 130 aa, sharing 88 aa at the N-terminus. The IEP's suggest a nuclear localization of the proteins. Surprisingly mRNA for the new gene was detected only in the salivary gland, but not in other adult human tissues and a restricted panel of embryonic tissues. The same holds true for a panel of human tumor cell lines and cell lines derived from ductal mammary carcinoma. RT-PCR revealed expression of PKW in 4 out of 11 breast carcinomas.

Amino Acid Sequence↗

PubMedDate not supplied

Identification of THW, a putative new tumor suppressor gene.

Differential Display between metastasizing and non-metastasizing human melanoma cell lines NMCL-1 and 530 led to the identification of a putative transmembrane receptor, designated as THW, which is down-regulated in the metastasizing cell line. THW is composed of 193 aa, exhibits four putative transmembrane domains and does not reveal any homology to other proteins. Down-regulation of THW is correlated with metastatic capacity of melanoma cell lines. THW was down-regulated in mammary carcinoma cell lines compared with cell lines derived from non-malignant mammary epithelium, in pancreas cell lines derived from metastases compared with a cell line derived from a primary tumor and in several tumor tissues compared with normal tissues. The function of THW as a tumor suppressor is emphasized by the location of the THW gene on chromosome 6q. LOH for this region has been reported in malignant melanoma and prostate, pancreas, uterine and mammary carcinomas.

Amino Acid Sequence↗

PubMedDate not supplied

Loss of heterozygosity of gene THW is frequently found in melanoma metastases.

We have recently described a new member of the PMP22/gas3 family of plasma membrane proteins referred to as THW. This gene is located on chromosome 6q and preliminary data have indicated a possible tumor suppressor gene function. We have therefore investigated LOH for gene THW in a panel of cancer cell lines and in a series of primary human melanomas as well as in melanoma metastases. We have detected LOH for gene THW in cell lines derived from melanoma, breast, pancreas, cervical, prostate and colon carcinoma with different prevalence, whereas the ovary carcinoma cell lines (n = 3) were negative. For melanomas we found a prevalence of LOH for gene THW of 10-20% in primary tumors, whereas in melanoma metastases we found a score of 50%. These data and the fact that the recently identified murine homologue PERP of gene THW mediates cell death in murine fibroblasts support the possible tumor suppressor function of gene THW.

Amino Acid Sequence↗

PubMedDate not supplied

Application of an enzyme-immunoassay (EIA) for rapid screening of 5 alpha-pregnane-3,20-dione (DHP) in blood plasma of the Asian elephant, Elephas maximus.

Populations of African (Loxodonta Africana) and Asian Elephants (Elephas maximus) in zoos and safari parks are at risk due to their low reproductive success. To extend the limited knowledge of their reproductive physiology, the development of easy and practical methods for the analysis of the relevant reproductive hormones is essential to support e.g. assisted reproduction. For the measurement of 5 alpha-pregnane-3,20-dione (DHP), the predominant ovarian gestagen in both species, an enzyme-immunoassay (EIA) based on commercial reagents was applied. Advantages of this EIA are the small volume of plasma needed for evaluation (5 microliters) and the possibility of direct processing without an extraction stage. The lower limit of detection was 0.16 ng/ml, the mean recovery was 101% and the mean coefficients of variation were 7.3% (intra-assay) and 9.9% (inter-assay). In Asian elephants, DHP levels reached 15 ng/ml during the luteal phase and up to 21 ng/ml during pregnancy. Estrous cycle lengths based on the lowest DHP concentrations varied from 12 to 20 weeks (mean 15.4 +/- 2.3). In two Asian elephant cows a calf was still-borne. Thereafter, the animals reassumed ovarian activity after approximately 8 and 13 weeks, respectively. In one animal estradiol implants for hormonal contraception caused a down regulation of the ovarian function as demonstrated by an irregular pattern of DHP secretion over a period of 48 weeks. We propose the direct DHP-EIA as a suitable method for reproductive monitoring in elephants, as it can be easily established in laboratories.

Animals↗

PubMedDate not supplied

Identification of metastasis-associated genes by transcriptional profiling of a metastasizing versus a non-metastasizing human melanoma cell line.

In order to identify genes associated with the metastatic phenotype we have compared the expression pattern of 6800 genes in a metastatic (NMCL-1) versus a non-metastatic (530) human melanoma cell line making use of DNA microarrays. The differentially expressed genes identified are involved in control of transcription, regulation of the cell-cycle, proteolysis, cell adhesion, immune response and signaling. A remarkable feature of the system under investigation is the consistent down-regulation of MHC-related and cell adhesion mediating genes in the metastatic cell line.

Animals↗