The development of cancer is due to the accumulation of multiple somatic mutations and in some cases due to germline mutations, which occur in malignancies such as retinoblastoma and Wilm’s tumor [1, 2]. Genetic alterations or changes in the expression of growth regulatory genes can lead to the initiation of malignant transformation and to eventual tumor progression [3-51. Cells that have undergone these cumulative alterations in either the structure or expression of these regulatory genes generally possess a selective growth and/or metastatic advantage over other non-transformed cells. In this context, oncogenes were originally detected in the genome of acutely transforming retroviruses. Their cellular homologs, proto-oncogenes, are important regulatory genes that are evolutionarily conserved since they are involved in controlling various aspects of cell growth and differentiation in invertebrates and vertebrates [6-81. Activation of dominantly transforming oncogenes by point mutations, gene amplification, chromosomal translocation or insertional mutagenesis can lead to uncontrolled cellular growth or to a disruption in normal differentiation or apoptosis [6, 9, 10]. Equally contributory to the process of malignant progression is the inactivation of recessive tumor suppressor genes due to point mutations and/or a loss of heterozygosity (LOH) in one allele, which can ultimately lead to a reduction to homozygosity in both alleles. This effect may be particularly deleterious since these genes, which include NF-1, APC, MSH2,~ 53 and Rb-1, can function as negative effecters of proteins that are involved in signal transduction, transcription regulatory proteins DNA repair [1, 2, &l l-131. The inappropriate activation or loss of expression of several of these genes in a stem cell population by the carcinogenic action of radiation, chemicals, hormones or viruses may lead to the clonal expansion of a subpopulation of stem cells that could exhibit aberrant growth and/or differentiation characteristics [3]. Growth factors and growth inhibitors are peptides that are involved in regulating normal cellular proliferation and differentiation and that are important in initiating and/or maintaining cellular transformation [14-161. Their activity or expression can be controlled by various oncogenes and tumor suppressor genes. Reciprocally, these peptides can regulate the activity or expression of specific oncogenes or tumor suppressor genes that are involved in the intracellular signal transduction pathway for these agents. In general, tumor cells exhibit a reduction in their requirement for exogenously supplied growth factors to maintain their proliferation. This relaxation in growth factor dependency as compared to non-transformed cells may be due in part from the ability of tumor cells to synthesize and respond to endogenously produced growth factors. These tumorderived growth factors might function via an intracrine, juxtacrine, autocrine or paracrine mechanism to control cellular proliferation in cells that are also expressing cognate receptors for these peptides [15-171. In this regard, the enhanced expression of different endogenous growth factor or inhibitor genes such as transforming growth factor (Y (TGFa), TGF& platelet-derived growth factor (PDGF), tibroblast growth factors (FGFs) and the insulin-like growth factors (IGFs) may be involved in mediating some of the biological effects that are. produced in transformed cells following activation of protooncogenes. For example, overproduction of peptides such as TGFa, IGF-1 or basic FGF in appropriate expression vectors can induce a transformed phenotype in various mesenchymal and epithelial cells in vitro and in vivo [16,171 …