In view of the pleiotropic growth characteristics of even subsets of colo- rectal tumor cells it seems doubtful whether any single molecular markers can be identified that may serve as prognostic indicators. It is conceivable, however, that a set of molecules, each one of which may individually lack predictive value, can form a distinctive quantitative pattern that is informative with regard to the progression of a colo-rectal tumor. Recently, a computer-based, high resolution, quantitative two- dimensional gel electrophoresis system (the QUEST system) has been used to resolve and quantitate more than 2000 cellular proteins in several rat cell lines such that defined sets of proteins whose quantitative expression vary under different growth conditions have been identified. This technology seems eminently well suited to record quantitative differences in individual proteins expressed by colo-rectal tumors. It is proposed that a characterization by the QUEST system of carefully selected colon carcinoma cell lines will provide a protein database consisting of well over 2000 proteins, whose quantitative expression in different cell lines corresponding to defined tumor stages will allow the identification of sets of candidate marker proteins. Such proteins will be characterized as to molecular weight, pI, glycosylation, membrane integration and subcellular localization. Some if not all of these proteins will be molecularly cloned using the QUEST system in the screening procedure and oligonucleotide probes and peptide antisera will be prepared such that the expression of the cloned proteins can be assessed in colo-rectal tumor biopsies. The growth characteristics of colo-rectal tumor cells are obviously controlled by a variety of factors. It is conceivable that one of these factors is the role of the immune system. The recent observation that class I major histocompatibility complex (MHC) antigens are induced in a variety of cells following treatment with DNA damaging agents suggests that measurements of such antigens may be of predictive value in the chemotherapy of colo-rectal tumors. The induced expression of class I MHC antigens seems to involve the non-polymorphic genes, whose function is unknown but whose structure suggests that the gene products may be target structures for some subset of cytotoxic T lymphocytes. It is proposed that oligonucleotide and antibody probes specific for individual, non-polymorphic class I antigens should be prepared and that the predictive value of such probes used on frozen sections of colo-rectal tumor biopsies should be evaluated.
| Shukla, H; Gillespie, G A; Srivastava, R et al. (1991) A class I jumping clone places the HLA-G gene approximately 100 kilobases from HLA-H within the HLA-A subregion of the human MHC. Genomics 10:905-14 |
| Shukla, H; Swaroop, A; Srivastava, R et al. (1990) The mRNA of a human class I gene HLA G/HLA 6.0 exhibits a restricted pattern of expression. Nucleic Acids Res 18:2189 |
