| First Author | Drosten M | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 3 | Pages | 707-718 |
| PubMed ID | 27872088 | Mgi Jnum | J:239406 |
| Mgi Id | MGI:5828697 | Doi | 10.1158/0008-5472.CAN-16-2925 |
| Citation | Drosten M, et al. (2017) H-Ras and K-Ras Oncoproteins Induce Different Tumor Spectra When Driven by the Same Regulatory Sequences. Cancer Res 77(3):707-718 |
| abstractText | Genetic studies in mice have provided evidence that H-Ras and K-Ras proteins are bioequivalent. However, human tumors display marked differences in the association of RAS oncogenes with tumor type. Thus, to further assess the bioequivalence of oncogenic H-Ras and K-Ras, we replaced the coding region of the murine K-Ras locus with H-RasG12V oncogene sequences. Germline expression of H-RasG12V or K-RasG12V from the K-Ras locus resulted in embryonic lethality. However, expression of these genes in adult mice led to different tumor phenotypes. Whereas H-RasG12V elicited papillomas and hematopoietic tumors, K-RasG12V induced lung tumors and gastric lesions. Pulmonary expression of H-RasG12V created a senescence-like state caused by excessive MAPK signaling. Likewise, H-RasG12V but not K-RasG12V induced senescence in mouse embryonic fibroblasts. Label-free quantitative analysis revealed that minor differences in H-RasG12V expression levels led to drastically different biological outputs, suggesting that subtle differences in MAPK signaling confer nonequivalent functions that influence tumor spectra induced by RAS oncoproteins. Cancer Res; 77(3); 707-18. (c)2016 AACR. |
