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Research was conducted to test whether the tumor suppressor gene product , p19(super Arf) hinders oncogenic transformation in primary cells and whether its role is abrogated when p53 is neutralized by viral oncoproteins and dominant-negative mutants. Cell cultures were monitored and maintained by calcium phosphate using the same amounts of DNA as in p53 degradation. Results showed high levels of genetic instability in p53 and that potent tumor suppressor activity resulted from the encoding of unrelated antioncogenic proteins with cooperating modes of action.

Several types of receptor-driven pathways are involved in oncogenesis. These are the receptor protein-tyrosine kinases, the Wnt/wingless pathway, cadherins and catenins, the Hedgehog/Patched/Smoothened pathway, the Notch pathway, cytokine rceeptors and TGF(beta) receptor and downstream signaling components. Activated forms of several components of the ERK MAP kinase pathway are oncoproteins, but new mitogenic signaling pathways have also been involved in tumorigenesis. These oncoproteins play a significant role in cell cycle progression and preventing apoptosis.

The P53 gene mediates apoptosis in cells with activated oncogenes, thus reducing the incidence of cancers. p53-mediated apoptosis slows tumor growth significantly as a T antigen mutant that cannot inactivate p53 functions in these cells is used. In senescence, p53 reacts to signals from normal cells undergoing progressive passages in culture. In late-passage cells, p53 activity and p21 levels increase, slowing or stopping the division rate of the culture. The lifespan of such cells is substantially enhanced with the addition of a transdominant-acting p53 mutant.

Experimental analysis of several naturally occurring and truncation tumor suppressor gene p53 mutants reveals a direct relation between p53-induced growth suppression and transcription activation. However, the mutants are capable of transactivation and transformation activities, indicating that p53 genes do not affect transformation. Cell lines containing the expression of endogenous p53 transactivating functional proteins have a high p53 transcriptional activity.

D-type cyclins mediate the cell cycle modulation of tumor suppressor protein Rb, which is hypophosphorylated in the G1 phase. The underphosphorylation of Rb stops cells in the G1 phase and the inhibition is eliminated by its phosphorylation. CDK4, a cyclin D partner, participates in G1 progression and carcinogenesis. Cells with CDK4 overexpression exhibit resistance to cell cycle arrest by growth inhibitors.

An untranslated area of mRNA can act as a tumor suppressive agent. A 0.2 kilobyte RNA from alpha-tropomyosin (Tm) 3' untranslated region (UTR) deters the development of cancerous cells. These cancerous cells become inactive upon constant expression of Tm 3'UTR.

Tumor suppressor genes play an important role in colon carcinogenesis. These genes helped identify intermediates in the progression pathway called the adenomatous polyp. Observations concerning the frequent loss of heterozygosity of DNA marker loci on chromosome 18q in colon tumors have also been associated with the genes. Moreover, tumor repressor genes function as an intermediate in the discrimination between initiating events and progression events.

Two class B synthetic multivulva (synMuv) genes, lin-35 and lin-53, in one of the two functionally redundant pathways of Caenorhabditis elegans are characterized. The purpose of this exercise is to study the molecular processes that determine how SynMuv genes constrain vulval induction. Results of the analysis reveal that vulval development in pathways mediated by the tumor suppressor Rb in C. elegans serves as antagonist of the receptor tyrosine kinase/Ras pathway of vulval induction.