Viruses tumour

Reverse transcriptase (from avian or murine RNA tumour viruses) [9068-38-6] [EC 2.7.7.49]. Purified by solubilising the virus with non-ionic detergent. Lysed virions were adsorbed on DEAE-cellulose or DEAE-Sephadex columns and the enzyme eluted with a salt gradient, then chromatographed on a phosphocellulose column and enzyme activity eluted in a salt gradient. Purified from other viral proteins by affinity chromatography on a pyran-Sepharose column. [Verna Biochim Biophys Acta 473 1 7977 Smith Methods Enzymol 65 560 1980 see commercial catalogues for other transcriptases.]... 

Calberg-Bacq, C.-M. Francois, C., Gosselin, L., Osterrieth, P. M. and Rentier-Delrue, F. 1976. Comparative study of the milk fat globule membrane and the mouse mammary tumour virus prepared from the milk of an infected strain of Swiss albino mice. Biochim. Biophys. Acta 419, 458-478. 

Baltimore D (1970) RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature 226 1209-1211... 

Fig. 5. Specificity of steroid response element. A. In this example (mouse mammary tumour virus), the element will bind receptors for glucocorticoids (G), androgen (A), progestin (P) and mineralocorticoid (M) so that each of these classes of steroid stimulate transcription. This type of specificity can vary from cell to cell possibly due to other protein factors (not shown). B. Although oestrogen (E) receptor will not act as an agonist for mouse mammary tumour virus transcription, it may antagonise the agonist activity of glucocorticoids (G).

It has now been found that the glucocorticoid response elements of mouse mammary tumour virus and the gene for chicken lysozyme also bind progesterone re-... 

As pointed out above, nt1 receptors have been discovered in lymphoma cells selected for resistance to the cytolytic glucocorticoid effect. Since receptors from which the M domain had been eliminated by cDNA manipulation still function to some extent in transfection studies it was important to find out whether nt1 receptors would also be able to mediate some hormonal response. This was in fact observed when nt lymphoma variants were transfected with a DNA construct consisting of the LTR region of the mouse mammary tumour virus coupled to the gene for chloramphenicol acetyltransferase (U. Gehring and H. Losert, unpublished experiments). Hormonal induction of enzyme activity was consistently observed but was low, as one might expect. 

As has already been mentioned, some lipophilic rifamycins and some strepto-varicins and geldanamycins affect the growth of cells transformed by RNA tumour viruses or the RNA-dependent DNA polymerase (reverse transcriptase) characteristic of these viruses. Again, high drug concentrations are needed to produce an effect and only partial, but never absolute, selectivity of enzyme inhibition has been found. 

Tumour cells also can arise by non-genetic means through the actions of specific tumour viruses. Tumour viruses are of two distinct types, those with DNA genomes (e.g. papilloma and adenoviruses) and those with RNA genomes (termed retroviruses). RNA tumour viruses are common in chickens, mice and cats but rare in humans. The only currently known human retroviruses are the human T-ceU leukaemia viruses and the related retrovirus (see Chapter 15). 

Cellular transformation by DNA tumour viruses in most cases has been shown to be the result of protein-protein interaction. Proteins encoded by the DNA tumour viruses, termed tumour antigens (T antigens), can interact with cellular proteins. This interaction effectively sequesters the cellular proteins away from their normal functional locations within the cell. The predominant types of protein sequestered by viral T antigens have been shown to be of the tumour-suppressor type. It is the loss of their normal suppressor functions that results in cellular transformation. 

About 20% of all cancers have been traced to tumour viruses, although the number of people infected is probably much larger than the number of people who actually develop cancer. Moreover, cancer-causing viruses may only be one of many contributing factors. DNA tumour viruses are probably more important as cancer-causing agents than RNA retroviruses (Table 17.1). 

Stow, N. D., Murray, M. D., and Stow, E. C. (1986). In Cancer Cells, Vol. 4 DNA Tumour Viruses Control of Gene Expression and Replication (M. Botchan, T. Grodzicker, and P. Sharp, Eds.), pp. 497-507. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. 

Conditions for optimal recoveries of poly(A) containing RNA, with minimal contamination from rRNA, were investigated. The poly(A) fractions isolated were effective as an RNA template for the synthesis of complementary DNA with the RNA-dependent DNA polymerase of avian myeloblastosis virus. Poly(dT)-cellulose has also been used both in the purification of a 14 S messenger RNA for the immunoglobulin light chain from microsomes of MOPC 41 mouse myeloma that appeared to code for a precursor protein [117], and in the purification of RNA-dependent DNA polymerase from RNA tumour virus [118]. An example of the use of oligo(dT)-cellulose is provided by the purification of a viral specific RNA from sarcoma virus-transformed nonproducer cells [119]. 

McCance, D. J. (1998) Human Tumour Viruses. ASM Press, Washington, DC. 

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