Cells, Cultured

Publication Title: 
International Journal of Cancer. Journal International Du Cancer

Dermal fibroblasts from patients with the autosomal dominant cancer-prone disease Basal Cell Nevus Syndrome (BCNS) exhibit a serum dependence, anchorage dependence and in vitro lifespan (about 20 population doublings or less) similar to those of fibroblasts from normal age-, race- and sex-matched controls.

Author(s): 
Shimada, T.
Dowjat, W. K.
Gindhart, T. D.
Lerman, M. I.
Colburn, N. H.
Publication Title: 
Journal of Cellular Biochemistry

Tumor-promoting phorbol esters, like growth factors, elicit pleiotropic responses involving biochemical pathways that lead to different biological responses. Genetic variant cell lines that are resistant to mitogenic, differentiation, or transformation responses to tumor promoters have been valuable tools for understanding the molecular bases of these responses.

Author(s): 
Colburn, N. H.
Smith, B. M.
Publication Title: 
In Vitro Cellular & Developmental Biology: Journal of the Tissue Culture Association

Human microvascular endothelial cells (HMVEC) from adult adipose tissue were cultured in MCDB 131 medium supplemented with 10% fetal bovine serum. Under these conditions, HMVEC from seven different donors had finite proliferative life spans ranging from 14.5 to 23.5 population doublings (PD), with a mean life span of 19 PD. Addition of 10% conditioned medium from activated human leukocyte cultures (BM Condimed) extended the life span of HMVEC to 31 to 41 PD, with a mean life span of 37 PD.

Author(s): 
Stein, G. H.
St Clair, J. A.
Publication Title: 
Experimental Cell Research

SV40 T-antigen-expressing human cells generally have an extension of lifespan until a period called "crisis" begins. On rare occasions a clone of cells emerges from the population in crisis and gives rise to an immortalized cell line. The present study compares the frequency of immortalization of cells from two different human lineages, lung fibroblasts and mammary epithelial cells.

Author(s): 
Shay, J. W.
Van Der Haegen, B. A.
Ying, Y.
Wright, W. E.
Publication Title: 
Oncogene

This study addresses the question of whether loss of p16INK4 expression contributes to the immortalization of human cells. In vitro immortalization usually proceeds through two phases. In the first phase (lifespan extension), cells continue proliferating and their telomeres continue shortening beyond the point at which normal cells become senescent. In the second phase (immortalization), the cells activate a telomere maintenance mechanism and acquire an unlimited proliferative potential.

Author(s): 
Noble, J. R.
Rogan, E. M.
Neumann, A. A.
Maclean, K.
Bryan, T. M.
Reddel, R. R.
Publication Title: 
The EMBO journal

Telomere loss has been proposed as a mechanism for counting cell divisions during aging in normal somatic cells. How such a mitotic clock initiates the intracellular signalling events that culminate in G1 cell cycle arrest and senescence to restrict the lifespan of normal human cells is not known. We investigated the possibility that critically short telomere length activates a DNA damage response pathway involving p53 and p21(WAF1) in aging cells.

Author(s): 
Vaziri, H.
West, M. D.
Allsopp, R. C.
Davison, T. S.
Wu, Y. S.
Arrowsmith, C. H.
Poirier, G. G.
Benchimol, S.
Publication Title: 
Cancer Research

Inactivation of p16INK4 tumor suppressor gene function is frequently observed in breast cancer. We examined p16INK4 expression in human mammary epithelial cell (HMEC) cultures established from four normal donors. Normal HMECs divide a limited number of times before proliferation ceases in a state referred to as selection (or M0). The cell subpopulation that emerges spontaneously from selection undergoes a further limited period of proliferation before senescence.

Author(s): 
Huschtscha, L. I.
Noble, J. R.
Neumann, A. A.
Moy, E. L.
Barry, P.
Melki, J. R.
Clark, S. J.
Reddel, R. R.
Publication Title: 
Developments in Biological Standardization

SV40 infection of human cells results in both transformation and lytic infection. We have used origin-defective viral mutants which are unable to replicate in permissive cells to help analysis of transformation. Expression of large T antigen (T ag) and small t antigen results in the altered growth phenotypes characteristic of transformation in other species. Human diploid fibroblasts (HF) have a limited lifespan and undergo senescence; T ag results in extension of lifespan but only in rare cases are the cells capable of continuous growth and are immortal.

Author(s): 
Kim, S. H.
Banga, S.
Jha, K. K.
Ozer, H. L.
Publication Title: 
Mechanisms of Ageing and Development

Carnosine (beta-alanyl-L-histidine), an abundant naturally-occurring dipeptide has been shown to exhibit anti-ageing properties towards cultured cells, possibly due in part to its antioxidant/free radical scavenging abilities. In this paper the results of an investigation on the effects of carnosine, at the physiological concentration of 20 mM, on oxidative DNA damage levels and in vitro lifespan in peripheral blood derived human CD4+ T cell clones are reported.

Author(s): 
Hyland, P.
Duggan, O.
Hipkiss, A.
Barnett, C.
Barnett, Y.
Publication Title: 
Cancer Research

The vast majority of breast cancers are carcinomas that arise from mammary epithelial cells (MECs). One of the key early events in tumorigenic transformation is the ability of cells to overcome replicative senescence. However, the precise genetic changes that are responsible for this event in MECs is largely unknown. Here, we report that Bmi-1, originally identified as a c-Myc cooperating oncoprotein, can bypass senescence, extend the replicative life span, and immortalize MECs. Furthermore, Bmi-1 was overexpressed in immortal MECs and several breast cancer cell lines.

Author(s): 
Dimri, Goberdhan P.
Martinez, Jose-Luis
Jacobs, Jacqueline J. L.
Keblusek, Petra
Itahana, Koji
Van Lohuizen, Maarten
Campisi, Judith
Wazer, David E.
Band, Vimla

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