Hyperplasia, hyperkeratosis and benign tumor production in transgenic mice by a targeted v-fos oncogene suggest a role for fos in epidermal differentiation and neoplasia.
A vector, derived from the human K1 keratin gene, has been employed to target v-fos expression exclusively in the epidermis of transgenic mice. Adult transgenic mice expressors (3-4 months) displayed hyperplasia and hyperkeratosis, initially in wounded (tagged) ears, which later became bilateral. This phenotype appeared at other epidermal sites, most notably in the axilla and inguinal areas. This indicates that a second promoting event, such as wounding or friction, is required to elicit these pathological changes. Highly keratotic benign ear lesions and benign squamous papillomas appeared after long latency at sites of phenotypic epidermis. These data suggest that v-fos may be interfering with c-fos function in normal keratinocyte differentiation, but by itself is insufficient to elicit overt benign lesions.
Greenhalgh
D A
DA
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Rothnagel
J A
JA
Wang
X J
XJ
Quintanilla
M I
MI
Orengo
C C
CC
Gagne
T A
TA
Bundman
D S
DS
Longley
M A
MA
Fisher
C
C
Roop
D R
DR
D000505:Alopecia / Q000209:etiology; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D004817:Epidermis / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D016762:Genes, fos; D006965:Hyperplasia; D007633:Keratins / Q000032:analysis; D007642:Keratosis / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016761:Oncogene Proteins v-fos / Q000032:analysis; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D012878:Skin Neoplasms / Q000235:genetics*
D016761:Oncogene Proteins v-fos; D016760:Proto-Oncogene Proteins c-fos; D007633:Keratins