Different malignant phenotypes induced in a stable, subdiploid, benign epithelial clone by DNA transfection.
Progression to malignancy in carcinomas has been studied in a stable, benign, subdiploid, cloned epithelial cell line (A5P/B10) sensitive to Geneticin at 100 micrograms/ml. A total of 28 cell lines were selected for Geneticin - resistance and inoculated into the footpads of syngeneic animals following co-transfection with pSV2neo and genomic DNA, or transfection with plasmid constructs containing neo and the activated Ha-ras oncogene. The behavior of 12 cell lines cotransfected with normal genomic DNA and inoculated into 146 footpads was the same as the A5P/B10 cells. Low grade primary tumors were produced in 122 footpads by 13 cell lines transfected with Ha-ras, and a proportion (61/122) produced well-differentiated lymph node metastases. One of 3 cell lines cotransfected with genomic DNA from a malignant cell line (BC1) produced 8 anaplastic primary tumors with anaplastic metastases. Cell lines from lymph nodes involved by these anaplastic tumors were sensitive to Geneticin, and genomic DNA from 2 clones of these cells failed to produce a malignant phenotype when co-transfected into the A5P/B10 cells. These results indicated that the progression to a malignant phenotype induced in benign cells from a spontaneous epithelial tumor by co-transfection with genomic DNA from malignant cells was different from that induced by the ras oncogene.
Gibbins
J R
JR
Department of Pathology, University of Sydney, Australia.
Nicholson
T R
TR
Vozab
R J
RJ
Ying
B
B
Messerle
K R
KR
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004273:DNA, Neoplasm / Q000235:genetics*; D004848:Epithelium / Q000473:pathology; D011905:Genes, ras; D005839:Gentamicins / Q000494:pharmacology; D006918:Hydroxyurea / Q000494:pharmacology; D008207:Lymphatic Metastasis; D008325:Mammary Neoplasms, Experimental; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D010957:Plasmids; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D004273:DNA, Neoplasm; D005839:Gentamicins; C010680:antibiotic G 418; D001374:Azacitidine; D013755:Tetradecanoylphorbol Acetate; D006918:Hydroxyurea