Cell Transformation, Neoplastic

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: 
Mutation Research

Human diploid fibroblasts, strain MRC-5, were sequentially irradiated with 60Co gamma rays at intervals during their in vitro lifespan. The results indicate that 3 or 6 doses of 1 Gy can increase lifespan, and the same was true for cells treated with 3 doses of 3 Gy. Higher doses (5 x 3 Gy) did reduce growth potential, suggesting either that mid-late passage cells become more sensitive to radiation, or that doses beyond a given threshold reduce population lifespan by multiple cellular hits. The life extension induced by gamma rays might be due to an induced hypermethylation of DNA.

Author(s): 
Holliday, R.
Publication Title: 
Critical Reviews in Oncogenesis

For several decades simian virus 40 (SV40) early region genes have been used as a means of generating immortalized human cell lines; however, the molecular mechanisms of this process have begun to be understood only recently. SV40-induced immortalization proceeds via two phases. In the first phase ("lifespan extension"), cells continue proliferating for a limited number of population doublings beyond the point at which normal cells undergo senescence.

Author(s): 
Bryan, T. M.
Reddel, R. R.
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: 
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: 
Annals of Medicine

The biology of telomeres and telomerase has been the subject of intensive investigative effort since it became evident that they play a significant role in two important biological processes, the loss of cellular replicative capacity inherent to organismal ageing and the unrestricted cell proliferation characteristic of carcinogenesis. Telomere shortening in normal cells is a result of DNA replication events, and reduction beyond a critical length is a signal for cellular senescence.

Author(s): 
Urquidi, V.
Tarin, D.
Goodison, S.
Publication Title: 
Oral Oncology

Odontogenic keratocysts (OKC) present an aggressive course with a marked tendency to recurrence. The epithelium of OKC is thought to have an intrinsic growth potential and has been shown to present a higher rate of proliferation as compared to other types of cyst. bcl-2 has a role in the extension of cell survival. The objective of the present study was to evaluate the bcl-2 protein expression in different odontogenic cysts. A total of 19 dentigerous cysts (DC), 20 radicular cysts (RC) and 14 OKC were used in the present study. DC and RC showed an almost complete negativity for bcl-2.

Author(s): 
Piattelli, A.
Fioroni, M.
Rubini, C.
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
Publication Title: 
Cancer Biology & Therapy

Studies were conducted to directly test whether the introduction of telomerase protects cancer-prone human mammary epithelial cells from chromosomal instability and spontaneous immortalization. Using a model for Li Fraumeni Syndrome (LFS), infection of human telomerase resulted in maintenance of telomere lengths, extension of in vitro lifespan, and prevention of spontaneous immortalization.

Author(s): 
Elmore, Lynne W.
Turner, Kristi C.
Gollahon, Lauren S.
Landon, Melissa R.
Jackson-Cook, Colleen K.
Holt, Shawn E.

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