Increased expression of mutated Ha-ras during premalignant progression in SENCAR mouse skin.
The ras proto-oncogene family products are membrane-associated, guanine nucleotide-binding proteins that serve as a molecular switch for signal transduction pathways in a diverse array of organisms. In the mouse skin two-stage carcinogenesis model, a specific point mutation in Ha-ras codon 61 is responsible for the initiation event. Here we investigated whether Ha-ras protein and mRNA expression change during premalignant progression. Also, we assessed the Ha-ras mutated allele after these changes. To those ends, we analysed the Ha-ras expression profiles in normal and hyperplastic skin, papillomas, and squamous cell carcinomas by western blotting, reverse transcription-polymerase chain reaction, and in situ hybridization. Increased levels of Ha-ras expression were observed at specific times during promotion. These changes were followed by an increase in the level of expression of the Ha-ras mutated allele. These results suggest that increased expression of Ha-ras mutated alleles may have an important role during premalignant progression.
Rodriguez-Puebla
M L
ML
The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, TX 78957, USA.
LaCava
M
M
Bolontrade
M F
MF
Russell
J
J
Conti
C J
CJ
D000483:Alleles; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics*; D051379:Mice; D018632:Mice, Inbred SENCAR; D009154:Mutation / Q000235:genetics*; D010212:Papilloma / Q000235:genetics / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
D012333:RNA, Messenger; D016283:Proto-Oncogene Proteins p21(ras)