Malignancy oncogenes

In acquired malignancies, oncogene activity appears to occur in association with chromosomal rearrangement. There is some evidence that the cooperation of two or more oncogenes, acting in concert, or in sequence, may effect transformation of a normal stale to a malignant one. However, further studies are needed to clarify this siiuation. 

Maio M, Coral S, Fratta E, Altomonte M, Sigalotti L. Epigenetic targets for immune intervention in human malignancies. Oncogene 2003 22 6484-6488. 

Gewirtz AM (1999) Myb targeted therapeutics for the treatment of human malignancies. Oncogene 18 3056-3062... 

Some established cell lines were derived from malignant tissue. Many of these cell lines can form tumors when injected into susceptible animals. Other established cell lines are not Uunorigenic. However, exposure to carcinogens, and irradiation can cause these cells to form tumors in susceptible animals. In addition, transformation can be caused by spontaneous mutations, by growth factors, and by viral (or oncogenic) transformation (Table 6). Malignant transformation is defined as consisting of the series of events that cause normal cells to develop the capacity to form tumors. 

Many vimses, both DNA and RNA containing, will cause cancer in animals. This so-called oncogenic achvity of a vims can be demonstrated by the observahon of tumour formahon in inoculated experimental animals and by the ability of the vims to transform normal tissue culture cells into cells with malignant characteristics. These transformed cells are easily recognizable as they exhibit such properties as rapid growth and frequent mitosis, or loss of normal cell contact inhibition, so that they pile up on top of each other instead of remaining in a well-organized layer. 

RNA oncogenic vimses have an unusual enzyme, reverse transcriptase, which is capable of making DNA copies from an RNA template. Cells transformed by these retrovimses have been shown to possess DNA transcripts of the viral RNA. It appears that the transformahon from normal to malignant is associated with the acquisition by the cell of viral DNA. 

Virally induced antigens result from a malignant transformation occurring in the cell, due to an oncogenic vims. These evoke powerful immune responses in experimental animals. 

Infection by viruses carrying oncogenes can cause malignant cell growth. Although first recognized as causative agents in avian cancers 90 years ago, for much of the twentieth century there was doubt that any human cancers were initiated in this way. Even now, almost all the information in this area refers to nonhuman animals, which presents a number of problems. First, as was already... 

Horinaka M, Yoshida T, Shiraishi T, et al. Luteolin induces apoptosis via death receptor 5 upregulation in human malignant tumor cells. Oncogene 2005 24 7180-7189. 

Resmethrin (I) Likely to be carcinogenic to humans based on increased incidences of benign and malignant liver tumors in female rats and male mice. A low-dose extrapolation approach was applied to the experimental animal data in order to estimate human cancer risk [100]. No oncogenic effects were seen [101]. 

Since a monoclonal antibody is a fusion product of a malignant mouse cell and an antibody-producing cell, there is some concern about the safety of the production process itself (Petricciani, 1983). Methods for the production of monoclonal antibodies raise two general safety issues (1) the theoretical risk of transferring in the product factors associated with malignancy (e.g., oncogene factors) and (2) the use of animals for antibody production that are known to harbor a number of microbial agents some of which can produce diseases in humans. 

G2. Garcia, M., Derocq. D., Pujol, P., and Rochefort, H., Overexpression of transfected cathep-sin D in transformed cells increases their malignant phenotype and metastatic potency. Oncogene S, 1809-1814 (1990). 

Wick, W., Fumar, F.B., Naumann. U., Cavenee, W.K., Weller, M. 1999, PTEN gene transfer in human malignant glioma sensitization to irradiation and CD95L-induced apoptosis. Oncogene 18 3936-3943. 

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