Partial suppression of tumorigenicity in a human lung cancer cell line transfected with Krev-1.
A human non-small-cell lung carcinoma cell line, Calu-6 (from an anaplastic carcinoma), was transfected with the Ki-ras-related anti-oncogene Krev-1. Several transfectant lines were obtained that showed a reduced tumorigenicity in nude mice with respect to the parental and control transfected cell lines. This decrease was approximately 50% in tumor incidence at 4 wk after subcutaneous inoculation of the transfected cells. In addition, the volume of the Calu-6 revertant-derived tumors was three to 10 times smaller than that of the equivalent tumors produced by inoculation of the control cell line transfected with the neomycin-resistance gene. Krev-1--transfected cells that exhibited reduced tumorigenicity expressed Krev-1 mRNA and had variable numbers of copies of the Krev-1 gene. Moreover, Krev-1--transfected cells exhibited a more differentiated squamous epithelial morphology than the parental and control cell lines did. Moderately elevated levels of protein kinase C activity were detected in some revertant clones. Such activity correlated with the level of expression of Krev-1 mRNA in most cases. In summary, Krev-1 induced important morphological and biological changes in transfected Calu-6 cells that we interpreted as partial reversion of the malignant phenotype.
Caamano
J
J
Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennyslvania 19111.
DiRado
M
M
Iizasa
T
T
Momiki
S
S
Fernandes
E
E
Ashendel
C
C
Noda
M
M
Klein-Szanto
A J
AJ
D000818:Animals; D015139:Blotting, Southern; D002455:Cell Division; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D016147:Genes, Tumor Suppressor; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011493:Protein Kinase C / Q000378:metabolism*; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D011493:Protein Kinase C