Biomedical subjects

S Farzad

Publications and source records attributed to S Farzad.

3 recordsLinked to original sources

PubMed1999

NS22: a highly polymorphic complex microsatellite marker within the ATM gene.

We have found a complex repeat sequence (NS22) that is highly polymorphic and located within intron 45 of the ataxia-telangiectasia gene (ATM). Sequencing this region from various individuals demonstrated two different polymorphic repeating units adjacent to one another. The fact that the sequence is located within the ATM gene provides a unique opportunity to follow segregation of affected and unaffected haplotypes for prenatal diagnosis of ataxia-telangiectasia. The high degree of polymorphism observed with this marker will also aid in evaluating loss of heterozygosity (LOH) across this region of the genome and may prove valuable in assessing the role of the ATM gene in susceptibility to cancer.

Ataxia Telangiectasia Mutated Proteins↗

PubMed1996

Expression of Epstein-Barr nuclear antigen 2 in kidney tubule cells induce tumors in transgenic mice.

The effect of EBNA2 in normal cells in vivo has not as yet been explored. The experiments described here were initiated to follow the consequences of the expression of EBNA2 in different tissues in transgenic mice. EBNA2 transgenic strains were generated using a vector containing EBNA2 encoding sequences under the control of the simian virus 40 (SV 40) early enhancer/promoter fused to the endogenous EBNA2 Wp promoter. Control mice carrying a transgene with the same sequence but lacking the EBV DNA part remained healthy during observation periods of up to 15 months. The SV-EBNA2 transgenic animals, however, over time developed abdominal masses that on necropsy showed to be due to kidney tumors. Histological examination revealed the presence of tumors with the morphology of kidney adenocarcinoma with a solid growth pattern. At the age of 20 weeks the kidneys of all animals investigated showed disseminated islands of tubular hyperplasia but no true malignant neoplasms. At about 50 weeks of age multiple foci of microscopic tubular adenocarcinomas were found in both kidneys. Eventually, tumors could be diagnosed in about 90% of the SV-EBNA2 transgenic mice. EBNA2-encoding RNA was expressed in both non-malignant kidney tissue and in tumors as shown by cDNA/PCR analysis. Immunoprecipitation and immunoblot analysis showed that the tumor cells contained a polypeptide of the same size as EBNA2 in B95-8 cells that reacted with a monoclonal anti-EBNA2 antibody. Immunohistochemistry demonstrated nuclear expression of EBNA2 in hyperplastic tubules and in tumor tissue.

Adenocarcinoma↗

PubMed1994

Response to cAMP levels of the Epstein-Barr virus EBNA2-inducible LMP1 oncogene and EBNA2 inhibition of a PP1-like activity.

The expression of the Epstein-Barr virus LMP1 oncogene is regulated by viral and non-viral factors in a tissue dependent fashion. The virus encoded transcription factor EBNA2 induces its expression in human B-cells. However, this induction also requires the contribution of cellular and/or other viral factors. In nasopharyngeal carcinoma cells and in cells from Hodgkin's lymphoma, LMP1 gene transcription is independent of viral products. Here we show that the effect of a factor binding to a cAMP responsive-like element (CRE) in the LMP1 gene transcription regulatory sequence (LRS) is essential for efficient promoter activity in the DG75 B-cell line and that elevation of cAMP levels in the cells induces LRS-derived CAT activity in a CRE dependent fashion. Incubation of two EBV-immortalized B-cell lines expressing endogenous EBNA2A with 8-Br cAMP increased the levels of the latency associated 66 kDa LMP1 within 2 h. Interestingly, LMP1 expression in DG75 cells conferred resistance to the inhibitory effect of 8-Br cAMP on cell proliferation. The protein phosphatase 1 and 2A (PP1 and PP2A, respectively) inhibitor okadaic acid also stimulated LRS-CAT activity in DG75 cells. EBNA2A from an EBV-immortalized B-cell line co-immunopurified with a PP1-like protein. An EBNA2A fragment spanning residues 324-436 fused to the GST protein specifically rescued a PP1/PP2A-like component from DG75 cell extracts. This GST-EBNA2A fusion product inhibited a PP1-like activity in nuclear extracts from these cells.

8-Bromo Cyclic Adenosine Monophosphate↗