Resistance of human cells to tumorigenesis induced by cloned transforming genes.

Abstract

The transformation of human cells was examined by transfection of cloned oncogenic DNAs derived from the tumor virus simian virus 40 and from the human bladder carcinoma cell line EJ into diploid fibroblasts derived from foreskin Modern cancer research has been caught for some years on the horns of a dilemma: the concept of neoplastic transformation in a single step based largely on the studies of tumor viruses in animal systems and the vast evidence, both clinical and experimental, of neoplasia as a multistage process. A synthesis of these opposing views has begun as a consequence of the availability of a new set of analytical reagents called oncogenes, which are cloned fragments of DNA with transforming activity.Oncogenes have been recognized by two kinds of experiments: identification by mutational analysis of transforming sequences in the genomes of avian and rodent retroviruses and identification of transforming sequences (in some instances related to retroviral transforming genes) in DNAs of tumor origin by their ability to induce oncogenic transformation of NIH/3T3 mouse cells (1). These experiments have been interpreted as support for the single-step origin of tumorigenicity, but the recipients being tested were either preneoplastic cells (e.g., NIH/ 3T3) that had already undergone unspecified genomic changes or animals infected with multifunctional viruses (i.e., containing long terminal repeats as well as transforming genes). Recently, transfection experiments using early passage rodent cells instead of established cell lines have implicated multiple oncogenes in animal cell culture models of neoplasia (2-4). These results herald a growing recognition among virologists that oncogenesis is a multistage process. The problem now is to identify the multiple stages in terms of specific genes and specific functions. As yet, neither the number nor the nature of essential functions required for tumorigenic transformation of rodent cells is known.Superimposed on this hiatus in our knowledge is the question of the appropriateness of rodent cells as model systems in

Creating oral squamous cancer cells: A cellular model of oral–esophageal carcinogenesis

“…Indications that the neoplastic transformation of human cells is even more complex came from numerous attempts to transform cultured normal human cells by introducing different genetic alterations. Invariably, such attempts failed (39,40). These failures suggested that human cells require an even greater number of genetic alterations than rodent cells for transformation to a neoplastic state.…”

Interferon-induced revertants of ras-transformed cells: resistance to transformation by specific oncogenes and retransformation by 5-azacytidine.

“…In view of our previous finding that IFN did hot cause reversion in NIH 3T3 cells transformed by the mutated EJras (cell line RS504) (33), it seems that induction of phenotypic reversion and acquisition of resistance to oncogenic transformation after IFN treatment involve different mechanisms. Cell-mediated resistance to transformation by ras has been observed in a variety of primary and established cultures (7,9,13,17,28,31).…”

Characterization of primary human fibroblasts transformed by human papilloma virus type 16 and herpes simplex virus type 2 DNA sequences

“…These differences were not merely due to higher levels of plasmid DNA uptake in R-30 cells since both cell types contained similar levels of DNA at 48 h posttransfection (data not shown). When H-ras, an activated cellular oncogene, was transfected into R-30 cells or N-16 (Newbold & Overell, 1983;Sager et al, 1983), it appears that R-30 and N-16 cells do not behave like immortalized …”

“…This conclusion is based on the fact that H-ras alone or HSV-2 transforming fragments were unable to stably transform R-30 cells (Table 1). Several studies have demonstrated that H-ras can transform established or immortalized cells but not primary human or rodent cells (Sager et al, 1983;Barbacid, 1987 and references therein). When H-ras or HSV-2 DNA fragments were cotransfected with HZIP-16, the resulting cell lines were distinct when compared to cells immortalized by HZIP-16.…”