Retroviral transduction of the human c-Ha-ras-1 oncogene into midgestation mouse embryos promotes rapid epithelial hyperplasia.
Infection of mouse embryos at 8 days of gestation with a replication-defective retrovirus carrying the human c-Ha-ras-1 oncogene led to efficient and rapid induction of hyperplastic lesions. Twenty-four percent of viable off-spring developed abnormal growths after infection with purified virus. The lesions contained a single integrated provirus and produced viral RNA and the Ha-ras oncogene product (p21). The latency period between the time of infection and appearance of the lesions suggested that secondary alterations in addition to activated ras were necessary for neoplasms to develop. The earliest and most abundant growths were cutaneous and appeared from 4 to 36 weeks of age, with a median of 4 weeks of age. A number of subcutaneous lesions also developed over the same time span but at a median of 18 weeks of age. The rapid development of cutaneous lesions in response to transduction of the ras oncogene contrasts with other studies in which adult skin required secondary treatment with promoters prior to ras induction of epithelial hyperplasia. These results demonstrate that infection of midgestation mouse embryos allows rapid analysis of oncogene potency in skin.
Compere
S J
SJ
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Massachusetts 02142.
Baldacci
P A
PA
Sharpe
A H
AH
Jaenisch
R
R
D000818:Animals; D002472:Cell Transformation, Viral; D004274:DNA, Recombinant / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D004622:Embryo, Mammalian; D004848:Epithelium / Q000473:pathology; D005260:Female; D011905:Genes, ras; D006801:Humans; D006965:Hyperplasia; D015151:Immunoblotting; D051379:Mice; D015689:Oncogene Protein p21(ras); D009856:Oncogene Proteins, Viral / Q000032:analysis; D011247:Pregnancy; D012367:RNA, Viral / Q000032:analysis; D012867:Skin / Q000473:pathology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D004274:DNA, Recombinant; D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D012367:RNA, Viral; D015689:Oncogene Protein p21(ras)