Biomedical subjects

R Narayanan

Publications and source records attributed to R Narayanan.

130 records · Page 8Linked to original sources

PubMedDate not supplied

Telomeres, telomerase and cancer: is the magic bullet real?

Nature recruited telomerase to compensate for the incomplete replication of chromosomal ends (telomeres). In higher organisms, telomeres are eroded at each cell division. Cancer cells frequently show chromosomal instability resulting in ring chromosomes, telomeric associations, and dicentric chromosomes. As a consequence of telomeric erosion, the ribonucleoprotein complex termed "telomerase" is reactive in a subpopulation of cells. Telomerase adds a hexameric repeat of the sequence 5' TTAGGG 3' to the ends of the chromosomes and hence stabilizes the telomeric length. Telomerase is active in vertebrates mostly in germ cells and the early stage embryo but is inactivated or repressed in somatic cells. Detection of telomerase activity in the overwhelming majority of advanced and metastatic human cancers but not in most somatic cells implies that telomerase-dependent immortalization could contribute to the malignancy. Future studies on the expression and regulation of the individual components of telomerase may enable us to clarify the diagnostic and therapeutic potential of telomerase in cancer.

Animals↗

PubMedDate not supplied

Transcription factor decoy approach to decipher the role of NF-kappa B in oncogenesis.

Antisense inhibition of the RelA subunit of NF-kappa B transcription factor (but not the NFKB1 subunit) causes pronounced inhibition of tumor cell growth in vitro and in vivo. Inhibition of either subunit, however, results in inhibition of the heterodimeric NF-kappa B complex in antisense-treated cells. Either of the subunits of NF-kappa B can form homo- or heterodimers with other members of the Rel oncogene family. In an effort to decipher the role of homo- vs heterodimeric NNF-kappa B in regulating tumor cell growth, we have used a decoy approach to trap these complexes in vivo. Using double-stranded phosphorothioates as a direct in vivo competitor for homo- vs heterodimeric NF-kappa B, we demonstrate that decoys more specific to RelA inhibit growth tumor cell growth in vitro. We demonstrate that RelA, either as a homodimer or a heterodimer with some other members of the Rel family and not the classical NF-kappa B (RelA/NFKB1), is involved in the differential growth control of tumor cells. Our results indicate that such transcription factor decoys can be a non-antisense tool to study the function of DNA-binding transcription factors.

Animals↗

PubMedDate not supplied

The NF-kappaB transcription factor in oncogenesis.

The NF-kappaB transcription factor complex is a pleiotropic activator that participates in the induction of a wide variety of cellular and viral genes. The active complex is composed of two subunits designated NFKB1 and RelA (formerly called p50 and p65, respectively). Binding sites for NF-kappaB are present in the promoter region of many cell adhesion molecules, cytokines and growth factors. Antisense inhibition of the individual subunits of NF-kappaB exerted differential effects on cell adhesion. Antisense phosphorothioate oligomers to relA but not NFKB1 caused a rapid inhibition of cell adhesion in diverse cell types. Antisense relA oligomers exerted antigrowth effects on diverse transformed cells in vitro and caused a pronounced inhibition of tumorigenicity in nude mice tumor models. Stable transfectants of a fibrosarcoma cell line expressing dexamethasone-inducible antisense RNA to relA also showed inhibition of in vitro growth and in vivo tumor development. In response to inducible expression of antisense RNA, a pronounced tumor regression was seen in nude mice. Use of a "decoy" approach to inhibit RelA function directly also caused inhibition of tumor cell growth in vitro and in vivo. Our results indicate that key regulatory molecules such as transcription factors can be selectively targeted for therapeutic intervention in cancer.

Animals↗

PubMedDate not supplied

Telomerase activity in normal human endothelial cells.

Telomerase, a ribonucleoprotein complex, adds hexameric repeats of 5' T T A G G G 3' to the ends of chromosomes called telomeres. Telomerase activity is present in germ cells but not in most somatic cells. An overwhelming majority of cancer cells show elevated levels of telomerase activity. Once thought to be cancer-cell specific, it is becoming apparent that many proliferating normal cells express telomerase activity. In this study, we demonstrate that normal human endothelial cells express telomerase activity: the activity is growth related. In quiescent, confluent cultures, the telomerase activity is repressed. Furthermore, the activity is lost upon subculturing of the endothelial cells in vitro. Finally, G2/M arrest induced by nocodazole treatment of endothelial cells abolished telomerase activity. Primary cultures of endothelial cells offer a powerful model to study the role, if any, of telomerase in normal cells.

Cell Cycle↗