Cellular Immortality

Colgin, L. M., and R. R. Reddel. 1999. Telomere maintenance mechanisms and cellular immortalization. Curr Opin Genet Dev 9(1) 97—103. 

Other species of hybridomas, including human, have been produced but are generally created by the use of viruses conferring cellular immortality. Artificial immunization of the donor is often not practical or ethical and so cell lines are often derived from peripheral lymphocytes obtained from individuals naturally immune to the target substance. Some human monoclonal antibody secreting cell lines have been derived from spontaneously occurring myelomas, but this line of approach frequently is unrewarding as the probability that the antibody will be one of interest is remote. 

Newbold RF (2002), The significance of telomerase activation and cellular immortalization in human cancer, Mutagenesis 17 539-550. 

HPV-16 encodes a set of early gene oncoproteins (E6 and E7) responsible for cellular immortalization. HPV types 16 and 18 E6 and E7 proteins are known to interact strongly with p53 and retinoblastoma (Rb) tumor suppressor gene products, respectively (2). The association of E6 with p53 marks this tumor suppressor for rapid ubiquitin-mediated proteolysis. Reduced levels of p53 prevent the cell from activating cell cycle arrest and/or induction of apoptosis in genetically mutated cells. 

In their 1985 Cell paper, Greider and Blackburn announced the discovery of an enzyme that extended the DNA at chromosome telomeres in the ciliate, Tetrahymena. Since then, there has been an explosion of knowledge about both the RNA and protein subunits of this unusual ribonucleo-protein enzyme in organisms ranging from the ciliates to yeast to humans. The regulation of telomerase is now understood to take place both at the level of synthesis of the enzyme and via the state of its substrate, the telomere itself The roles of telomerase in both cellular immortality and cancer are vibrant areas of current research. 

Cell Lines. Cell lines, derived from tissue of various species, are commercially available from tissue culture banks. These cell populations are immortalized in that they possess the capacity to permanently proliferate in culture. Such cellular models can be studied in short-term suspension (hours) or longer-term monolayer culture (days, weeks, months). Since cell lines have been extensively cultured or passaged for multiple generations, the degree or retention (or loss) of kidney-specific morphology and function is an important limitation that is not thoroughly addressed for a number of renal cell lines. One renal cell line that has been relatively well characterized is the pig kidney cell line, LLC-PK,. 

Since the human airway epithelial cells will be used as a paradigm for the transformation of different cell lines, the following descriptions will focus on primary airway epithelial cells. The generation and isolation of an immortalized cell line is relatively straightforward, but requires attention to detail. Generally, primary cultures of cells are isolated from tissue using mechanical and/or enzymatic cellular dissociation protocols [21, 88-90] (Appendix 1). 

Hayflick, L. 1997. Mortality and immortality at the cellular level. A review. 

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