Cooperation between v-fos and v-rasHA induces autonomous papillomas in transgenic epidermis but not malignant conversion.
Transgenic mice have been previously established that express v-rasHa or v-fos exclusively in the epidermis by means of a targeting vector based on the human keratin 1 gene (HK1). Epidermal expression of v-rasHa (HK1.ras) or v-fos (HK1.fos) resulted in hyperplasia, hyperkeratosis, and later, in benign tumors. To assess the potential for oncogene cooperation in vivo mating experiments were performed. Resultant HK1.fos/ras mice exhibited an obvious increase in the severity of neonatal and juvenile preneoplastic phenotypes, together with the immediate onset of tumorigenesis as compared to single oncogene sibling controls. The HK1.fos/ras tumors grew aggressively and often compromised the animals by 10-12 weeks. However, tumors remained benign as determined by histotype and specific keratin markers. These data indicate that v-fos can cooperate with an initiating v-rasHa phenotype to generate autonomous papillomas, but additional events are required for malignant conversion.
Greenhalgh
D A
DA
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Quintanilla
M I
MI
Orengo
C C
CC
Barber
J L
JL
Eckhardt
J N
JN
Rothnagel
J A
JA
Roop
D R
DR
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D016762:Genes, fos; D011905:Genes, ras; D005822:Genetic Vectors; D006801:Humans; D006965:Hyperplasia; D007438:Introns; D007633:Keratins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010212:Papilloma / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D016385:TATA Box
D017931:DNA Primers; D007633:Keratins