[Stimulation of differentiation of LIM 1215 large intestinal tumor cells during expression of the p53 exogenous antioncogene or the activated ras oncogene].
The ability of exogenous p53 tumor-suppressor and activated N-PAS oncogene to influence differentiation state of human colon carcinoma LIM 1215 cells and their derivatives with acquired resistance to actinomycin D or methotrexate was analysed Introduction of retroviral construct expressing human wild-type (wt) p53 into LIM 1215 cells induced electron microscopic manifestations of enterocytic differentiation, i.e. caused an increase in the numbers of cells with microvilli, desmosomes and glandular-like lumens. Mutations at codons 248 or 273, the most frequent p53 changes in primary colorectal cancer, partially abrogated the ability of p53 to stimulate differentiation of LIM 1215 cells. Human M-PASasp12 showed stronger stimulation of cell differentiation as compared to p53wt. Especially high proportion (> 80%) of cells possessing pronounced manifestations of columnar enterocytic differentiation was observed after introduction of PAS-expressing construct into methotrexate-resistant LIM 1215 cell subline that originally demonstrated higher maturation than parental cell line. In cell subline with two introduced genes, activated PAS and mutant p53His273, the number of differentiated cells was similar to that observed in cell culture containing only PAS-construct. However, these two sublines differed in the quantity of desmosomes as well as in carcino-embryonic antigen (CEA) expression. Comparison of expression of different electron microscopic features of cell differentiation and CEA expression in cell sublines selected for methotrexate-resistance and/or expressing exogenous constructs allows to suppose that p53 tumor-suppressor, PAS oncogene and dhfr gene amplification may lead to somewhat distinct differentiation states.
Raĭkhlin
N T
NT
Volodina
Iu L
IuL
Smirnova
E A
EA
Perevoshchikov
A G
AG
Chumakov
P M
PM
Kopnin
B P
BP
D002272:Carcinoembryonic Antigen / Q000032:analysis; D002454:Cell Differentiation / Q000235:genetics; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D003609:Dactinomycin / Q000627:therapeutic use; D003896:Desmosomes / Q000648:ultrastructure; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D008871:Microvilli / Q000648:ultrastructure; D009154:Mutation; D014407:Tumor Cells, Cultured
D002272:Carcinoembryonic Antigen; D003609:Dactinomycin; D008727:Methotrexate
Stimuliatsiia differentsirovki kletok raka tolstoĭ kishki linii LIM 1215 pri ékspressii ékzogennogo antionkogena p53 ili aktivirovannogo onkogena ras.