ras gene activation and aberrant expression of keratin K13 in ultraviolet B radiation-induced epidermal neoplasias of mouse skin.
Both papillomas and squamous cell carcinomas (SCC) induced in mouse epidermis by initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA) exhibit aberrant expression of a type I keratin, K13, that is normally characteristic of terminal differentiation of internal stratified epithelia. There is evidence that the aberrant expression of K13 depends on the presence of an activated ras gene in mouse epidermal keratinocytes (Sutter et al., Mol Carcinog 4:467-476, 1991). To assess the general validity of this hypothesis, we investigated both aberrant K13 expression and activation of each of the three members of the ras gene family in epidermal tumors induced in four different mouse strains (SKH-1 hr, SENCAR, BALB/c, and C3H/He) by chronic irradiation with ultraviolet (UV) B. The tumor collection comprised nine papillomas and 30 well or poorly differentiated SCC. Aberrant K13 expression occurred in only five of 39 tumors and was restricted to SCC of both types. This indicates that aberrant K13 expression in UV-induced epidermal tumors was intrinsically different from that in chemically induced tumors. Polymerase chain reaction analysis of the tumors for different point mutations in codons 12, 13, and 61 of the Ha-ras and Ki-ras genes and in codon 61 of the N-ras gene revealed that only one of the well differentiated tumors from a SKH-1 hr mouse exhibited a GGA-->GAA mutation in codon 12 of the Ha-ras gene. Although this tumor was also positive for aberrant K13 expression, such a correlation could not be made for the remaining K13-expressing tumors. This indicates that the activation of one of the members of the ras gene family is not a general prerequisite for the aberrant expression of K13 in mouse epidermal keratinocytes.
Sutter
C
C
German Cancer Research Center, Research Program II, Heidelberg.
Strickland
P T
PT
Mukhtar
H
H
Agarwal
R
R
Winter
H
H
Schweizer
J
J
D000818:Animals; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics* / Q000528:radiation effects*; D011905:Genes, ras / Q000235:genetics* / Q000528:radiation effects*; D007633:Keratins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics*; D010212:Papilloma / Q000209:etiology / Q000235:genetics*; D017354:Point Mutation; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*; D015533:Transcriptional Activation; D014466:Ultraviolet Rays
D007633:Keratins