The contribution of the E6 and E7 open reading frames of human papillomavirus type 6b (HPV6b) and HPV16 to immortalization of human keratinocytes was evaluated by using amphotropic recombinant retroviruses. The HPV16 E7 gene could immortalize primary human keratinocytes without the cooperation of the viral E6 gene; however, E6 was able to contribute significantly to the efficiency of the E7 imm...

Linear EBV genomes undergo a transition to the circular form characteristic of latency by 16-20 h post-infection. This transition requires that the infected cells be activated to the G1 stage of the cell cycle. Cellular proliferation and expression of the activation marker CD23 were not required. Nevertheless, 36 h post-infection, only cells expressing CD23 contained covalently closed, circular...

The immortalization of human cells is a critical step during tumorigenesis. In vitro, normal human somatic cells must overcome two proliferative blockades, senescence and crisis, to become immortal. Transformation with viral oncogenes extends the life span of human cells beyond senescence. Such transformed cells eventually succumb to crisis, a period of widespread cellular death that has been p...

As a major component of the epidermal tissue, a primary keratinocyte has served as an essential tool not only for the study of pathogenesis of skin-related diseases but also for the assessment of potential toxicities of various chemicals used in cosmetics. However, its short lifespan in ex vivo setting has been a great hurdle for many practical applications. Therefore, a number of immortalizati...

Normal somatic cells are able to divide only a limited number of times before they become senescent. The occurrence of intratumoral cell death and the need for clonal evolution mean that many more cell divisions are required for tumorigenesis than is possible unless cells breach the senescence proliferation barrier and become immortalized. Senescence may therefore be a major tumor suppressor me...

Cellular progression to malignancy appears to require a number of distinct steps in which genetic damage in key regulatory genes accumulates. Immortalization, or escape from senescence, is considered to be one of the first phenotypic changes. Ni2+ treatment of normal human kidney epithelial (NHKE) cells in vitro resulted in immortalization of the cells IHKE cells). The combined action of Ni2+ a...

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 ...

Biological activities of extracellular Epstein-Barr virus (EBV) from two laboratory strains, namely P3J-HR-1 (P-H) from Burkitt's lymphoma and B95-8 (B95) from infectious mononucleosis, were compared. Virus stocks from both sources contained approximately the same number of virions. Virus from the P-H line induced early antigen in six non-producer EBV-genome carrier cell lines; virus from B95 d...

Cellular immortalization is one of the prerequisite steps in carcinogenesis. By gene expression profiling, we have found that genes in the interferon (IFN) pathway were dysregulated during the spontaneous cellular immortalization of fibroblasts from Li-Fraumeni syndrome (LFS) patients with germ-line mutations in p53. IFN signaling pathway genes were down-regulated by epigenetic silencing during...

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 ...