GSE200607
Conditional expression of oncogenic KrasG12D and HrasG12D alleles in mouse keratinocytes reveals a dose dependent requirement for tumor formation.
The discovery that activation of the Hras gene was the driver mutation for tumor development in mouse skin treated with 7,12-dimethylbenz(a)anthracene illuminated the link between environmental and molecular carcinogenesis. Subsequent studies revealed that activating mutations in the closely related Kras gene could also drive skin tumor development and progression under certain conditions.  To address a head to head comparison of downstream signaling produced by each activated oncogene primary keratinocytes were isolated from the LSL-HrasG12D and LSL -KrasG12D C57BL/6J mouse models that carry conditionally expressed mutant alleles when a Lox-STOP-Lox segment is excised by Cre recombinase adenovirus treatment. Keratinocytes expressing two mutant alleles of HrasG12D (HH), only one mutant allele of HrasG12D (H), one mutant allele of KrasG12D (K) or one mutant allele of each (HK) were  evaluated for differences in downstream signaling, gene expression and the ability to form squamous papillomas orthotopically in vivo. Overall design: To further characterize what unique transcriptional changes could be attributed to tumorigenic versus non tumorigenic cultures, we subjected WT, H, K, HH, and HK keratinocyte cultures to RNA-seq analysis.