Oncogenes and anti-oncogenes

The study of oncogenes offers insights into many steps in signal transduction. Rapid progress is possible because of the combination of biochemistry and genetics--unique in vertebrate cell biology--the availability of specific clones and antibodies, sequence information, dominant mutants, and biochemical assays of function. The wealth of detail on oncogenes and proto-oncogenes continues to increase dramatically. Hopefully, in the next year or two some of the gaps will be filled in and all the steps along at least one pathway from the cell membrane to the nucleus will be understood.     

Oncogenes, anti-oncogenes and the immune response to cancer: a mathematical model.

We develop a mathematical model for the initial growth of a tumour after a mutation in which either an oncogene is expressed or an anti-oncogene (i.e. tumour suppressor gene) is lost. Our model incorporates mitotic control by several biochemicals, with quite different regulatory characteristics, and we consider mutations affecting the cellular response to these control mechanisms. Our mathematical representation of these mutations reflects the current understanding of the roles of oncogenes and anti-oncogenes in controlling cell proliferation. Numerical solutions of our model, for biologically relevant parameter values, show that the different types of mutations have quite different effects. Mutations affecting the cell response to chemical regulators, or resulting in autonomy from such regulators, cause an advancing wave of tumour cells and a receding wave of normal cells. By contrast, mutations affecting the production of a mitotic regulator cause a slow localized increase in the numbers of both normal and mutant cells. We extend our model to investigate the possible effects of an immune response to cancer by including a first order removal of mutant cells. When this removal rate exceeds a critical value, the immune system can suppress tumour growth; we derive an expression for this critical value as a function of the parameters characterizing the mutation. Our results suggest that the effectiveness of the immune response after an oncogenic mutation depends crucially on the way in which the mutation affects the biochemical control of cell division.     

Oncogenes

Genetic elements responsible for key steps in the conversion of normal cells to malignancy, initially identified in oncogenic viruses, have normal cellular origins. These normal cell genes, protooncogenes, are highly conserved in an evolutionary context, and this fact, along with other data on expression and product localization, are hypothesized to play an important role in growth and differentiation. The number of such genes is limited to perhaps two dozen and they can be subdivided into families, thus implying fine-tuning functions. The conversion of protooncogenes to oncogenes can be based on mutation or selective stimulation based on chromosomal alterations, e.g., translocations, loss of control elements, or insertion of active promoters. A class of control elements, designated antioncogenes, has been tentatively identified in certain familial malignancies. Data are accumulating on the chromosomal localization of both onco- and antioncogenes, justifying prospects of defining cancer at the molecular level.     

细胞凋亡（Apoptosis）与癌基因

细胞凋亡是细胞衰老、死亡过程的主要形式.最近研究发现有多种癌基因与抑癌基因参与细胞凋亡过程.因此目前认为癌基因与抑癌基因不仅控制细胞增殖、分化,而且调节细胞凋亡.细胞凋亡受阻或缺陷可能是肿瘤发生的基础之一.     

Oncogenes and avian development

In order to detect signs of oncogene activity and elucidate their possible role in avian ontogeny we implemented two different strategies. One was to detect either the protein product or messenger RNA in situ at various stages of development. The other was to try and disturb development with retroviruses carrying one or several oncogenes in their activated forms. Time- and tissue-specific expression of c-myc was apparently not related to particular phases of cell evolution, such as population amplification. Rather the presence of c-myc immunoreactive product at particular stages appeared to depend on cell types. c-myb and c-ets messenger RNAs were found expressed preferentially in the blood system, respectively in hemopoietic and differentiating endothelial cells. The developing embryo heart was found to be uniquely sensitive to the effect of retroviruses provided that two conditions were respected. The first was the injection of the virus or construct prior to E3.5. The second was the presence of the v-myc gene, whether alone or associated with one or several other v-onc. In such cases a large proportion (70%) of chick and all quail embryos developed multiple heart rhabdomyosarcomas within 10 days. In chickens the association of a second v-onc or of two others induced the formation of secondary tumors, whose type was determined by the nature of the other oncogene(s).(ABSTRACT TRUNCATED AT 250 WORDS)     

Oncogenes and human leukemias

Eukaryotic cells contain a family of genes termed "cellular oncogenes" or "proto-oncogenes," thought to regulate normal cell growth and development. In some circumstances, such as following transduction by retroviruses, activation of these genes causes tumors and leukemias in animals. Possible mechanisms of cellular oncogene activation include: 1) DNA point mutation, deletion or insertion, 2) gene amplification, 3) gene activation by internal rearrangement, chromosomal translocation or promoter insertion, 4) recombinative events resulting in the formation of novel chimeric genes, and others. In this review, we consider data which implicates cellular oncogene activation in the pathogenesis of leukemia in humans. We discuss possible mechanisms by which oncogene activation may induce leukemias, as well as potential diagnostic and therapeutic implications.     

Oncogenes in hematologic neoplasia

Proto-oncogenes are normal genes involved in cellular proliferation and differentiation. Structural alterations in these genes can convert them to oncogenes involved in the initiation or progression of malignancy. About 50 proto-oncogenes have been described and four different activation mechanisms are known. Proto-oncogene alterations specific for human hematologic malignancies are well characterized.