Recent studies have demonstrated the existence of specific genes, termed oncogenes, which may play a role in the etiology of cancer. The studies presented here have focused on one such oncogene, ...initially isolated from a rat neuroblastoma, which has been termed neu. The neu oncogene encodes a 185,000 dalton protein product, termed p185. A panel of monoclonal antibodies have been produced which react with domains of the p185 molecule that are expressed on the surface of murine cells transformed by an activated rat neu oncogene. These antibodies do not bind murine cells transformed by various other agents. There is significant antibody reactivity with the rat neuroblastomas from which activated neu genes have been obtained; these antibodies also react with a protein on non-transformed rat fibroblasts which appears to be the normal rat homologue of the p185 molecule encoded by the activated neu oncogene. Exposure of neu-transformed cells to p185-specific monoclonal antibodies in vitro results in the rapid and reversible loss of cell-surface and total cellular p185. Although not directly cytotoxic, exposure to anti-p185 monoclonal antibodies also causes neu-transformed cells to revert to a non-transformed phenotype, as determined by the capacity for anchorage-independent growth. This with great likelihood results from antibody-mediated down-modulation of cell-surface p185. Thus the p185 molecule plays an important role in maintenance of the transformed phenotype. In vivo treatment with any of several p185-specific monoclonal antibodies is able to significantly inhibit the tumorigenic growth of neu-transformed cells implanted into nude mice and syngeneic rats. Furthermore treatment with mixtures of monoclonal antibodies reactive with distinct domains of the p185 molecule results in synergistic anti-tumor effects and eradication of small tumor burdens in some animals. The administration of monoclonal antibodies reactive with cell-surface domains of an oncogene-encoded protein represents a novel and potentially efficacious approach to the therapy of neoplasia.
We have found that an I-J+ I-A- antigen-presenting cell (APC) is required for Ts3 activation in vivo. Together with the I-J restriction previously reported for Ts3 induction (Takaoki, M., M.-S. Sy, ...A. Tominaga, A. Lowy, M. Tsurifiji, B. Benacerraf, R. Finberg, and M. I. Greene, 1982, J. Exp. Med., 156:1325), it appears that this I-J+ APC is responsible for I-J restriction in the triggering of Ts3. This restriction may be exerted via a pre-Ts3 associative recognition of antigen and I-J encoded determinants, analogous to the T helper recognition of antigen in the context of I-A and I-E determinants.
37 - Cancer Genetics Green, Douglas W.; Drebin, Jeffrey A.
Surgical Research,
2001
Book Chapter
Cancer is a disorder of cellular growth resulting from the sequential accumulation of genetic alterations in a clonal population of cells. Chromosomal abnormalities have been associated with the ...development of cancer for over 100 years. Cancer cytogenetics refers to the identification of specific chromosomal abnormalities in cancer cells. These may be relatively simple abnormalities, such as chromosomal breakage, duplication, or loss, or may be complex reciprocal translocations among chromosomes. The goals of studying cancer cytogenetics are to identify specific regions of specific chromosomes that are reproducibly altered in the development of particular tumor types. The tremendous advances in molecular biology that have occurred over the past 50 years have led to the ability to clone, sequence, and study the function of specific genes. Cancer molecular genetics refers to the characterization at the DNA level of specific genes that play a role in the etiology of cancer. Advances in studying the molecular genetics of cancer have also led to advances in population and cytogenetic studies, in some cases by defining the specific gene that is responsible for an inherited cancer family syndrome or that resides at the site of a particular chromosomal abnormality.
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