Inducible activation of oncogenic K-ras results in tumor formation in the oral cavity.
Mouse models for cancer represent powerful tools to analyze the causal role of genetic alterations in cancer development. We have developed a novel mouse model that allows the focal activation of mutations in stratified epithelia. Using this system, we demonstrate that activation of an oncogenic K-rasG12D allele in the oral cavity of the mouse induces oral tumor formation. The lesions that develop in these mice are classified as benign squamous papillomas. Interestingly, these tumors exhibit changes in the expression pattern of keratins similar to those observed in human premalignant oral tumors, which are reflective of early stages of tumorigenesis. These results demonstrate a causal role for oncogenic K-ras in oral tumor development. The inducible nature of this model also makes it an ideal system to study cooperative interactions between mutations in oncogenes and/or tumor suppressor genes that are similar to those observed in human tumors. To our knowledge, this is the first reported inducible mouse model for oral cancer.
Departments of Molecular and Cellular Biology and Dermatology, Baylor College of Medicine, Room T 713, One Baylor Plaza, Houston, TX 77030, USA. ccaulin@bcm.tmc.edu
Carlos
C
Caulin
Thao
T
Nguyen
Mary A
MA
Longley
Zhijian
Z
Zhou
Xiao-Jing
XJ
Wang
Dennis R
DR
Roop
D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000473:pathology; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D011905:Genes, ras / Q000235:genetics*; D007633:Keratins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D010212:Papilloma / Q000235:genetics / Q000473:pathology; D012150:Polymorphism, Restriction Fragment Length; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007633:Keratins; D015689:Oncogene Protein p21(ras)