Inhibition of tumorigenicity in lung adenocarcinoma cells by c-erbB-2 antisense expression.
The lung carcinoma cell line Calu3, which overexpresses the c-erbB-2 oncogene, was stably transfected with antisense (AS) cDNA constructs encompassing different regions of the c-erbB-2 gene. Transfected cells were analyzed for their tumorigenic properties in vitro and in nude mice. Two independent clones, AS F1 (low erbB-2 expressor) and AS B12 (high erbB-2 expressor), as well as the polyclonal Calu3/AS 5', were selected for these analyses. In Calu3/AS 5' transfected cells and in the AS F1 clone, c-erbB-2 RNA and protein levels were lower than those detected in the parental cell line and the AS B12 clone. Anchorage-independent growth and tumor take were also significantly reduced. Furthermore, cells derived from primary tumors of Calu3/AS 5', AS F1 and AS B12 lost the AS c-erbB-2 DNA insert but retained the gene for G418 resistance. Our results suggest that a correlation between c-erbB-2 overexpression and tumorigenicity may exist in the Calu3 lung carcinoma cell line.
Casalini
P
P
Division of Experimental Oncology E, Istituto Nazionale Tumori, Milan, Italy.
Ménard
S
S
Malandrin
S M
SM
Rigo
C M
CM
Colnaghi
M I
MI
Cultraro
C M
CM
Segal
S
S
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D018734:Genes, erbB-2; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D016376:Oligonucleotides, Antisense