The Bmi-1 oncoprotein regulates proliferation and oncogenesis in human cells. Its overexpression leads to senescence bypass in human fibroblasts and immortalization of human mammary epithelial cells. In this study, we report that compared with normal nasopharyngeal epithelial cells (NPEC), Bmi-1 is overexpressed in nasopharyngeal carcinoma cell lines. Importantly, Bmi-1 was also found to be ove...

Epstein-Barr virus infects human B lymphocytes. The interaction between the virus and these cells has been the subject of investigation for over three decades. Recent in vitro and in vivo studies, reviewed here, are revealing the mechanisms by which EBV induces and controls proliferation through the expression of six viral nuclear proteins and two plasma membrane proteins. This genetic program ...

The hypothesis that rodent cells can be immortalized by the direct induction of a single mutation-like event was tested by initiating cultures of benzo(a)pyrene treated Syrian hamster embryo cells with low inocula and expanding these few cells maximally until senescence prevented further culturing or immortalization took place. According to the mutation hypothesis immortalization is hardly to b...

In normal human cells, telomeres shorten with successive rounds of cell division, and immortalization correlates with stabilization of telomere length. These observations suggest that human cancer cells achieve immortalization in large part through the illegitimate activation of telomerase expression. Here, we demonstrate that the rate-limiting telomerase catalytic subunit hTERT is expressed in...

Normal human somatic cells have a finite life span and undergo replicative senescence after a limited number of cell divisions. Erosion of telomeric DNA has emerged as a key factor in senescence, which is antagonized during cell immortalization and transformation. To clarify the involvement of telomerase in the immortalization of keratinocytes, catalytic subunit of telomerase (hTERT) expression...

The p53 protein has become a subject of intense interest since the discovery that about 50% of human cancers carry pS3 mutations. Muta tions in thep5J gene are the most frequent genetic lesions in breast cancer, suggesting a critical role lor p53 protein in normal mammary epithelial cell (MEO growth control. We previously demonstrated that abrogation of the p53 function by a cancer-derived p53 ...

Epstein Barr virus (EBV) is one of the most successful pathogens in humans with more than 95% human adult population persistently infected. EBV infects only and threatens these its potent growth transforming ability that readily allows for immortalization B cells culture. Accordingly, it also found around 1-2% tumors, primarily lymphomas epithelial cell carcinomas. Fortunately, however, our imm...

Senescence is generally defined as an irreversible state of G(1) cell cycle arrest in which cells are refractory to growth factor stimulation. In mouse embryo fibroblasts (MEFs), induction of senescence requires the presence of p19(ARF) and p53, as genetic ablation of either of these genes allows escape from senescence and leads to immortalization. We have developed a lentiviral vector that dir...

Basic helix-loop-helix (bHLH) DNA-binding proteins have been demonstrated to regulate tissue-specific transcription within multiple cell lineages. The Id family of helix-loop-helix proteins does not possess a basic DNA-binding domain and functions as a negative regulator of bHLH proteins. Overexpression of Id proteins within a variety of cell types has been shown to inhibit their ability to dif...

Primary human keratinocytes are useful for studying the pathogenesis of many different diseases of the cutaneous and mucosal epithelia. In addition, they can form organotypic tissue equivalents in culture that can be used as epidermal autografts for wound repair as well as for the delivery of gene therapy. However, primary keratinocytes have a finite lifespan in culture that limits their prolif...