Ppp6c deficiency accelerates K-ras G12D induced tongue carcinogenesis
Education and Research
Abstract
In Head and neck squamous cell carcinoma (HNSCC) that are HPV(-), EGFR/ERBB2, or EGFR1/3 alterations were most frequent among receptor tyrosine kinases. Kinase targets, such as HRAS, PI3CA, and PTEN, also showed mutations implying perturbed RTK/RAS/PI3K signaling in HNSCC carcinogenesis. Moreover, the tumor suppressor Trp53 was mutant in more than half of the HNSCCs that were HPV(-).
Here, we examined the effect of Ppp6c deficiency on tumorigenesis in mice with tongue-specific expression of K-rasG12D (K-mice) as well as in K-rasG12D mice deficient in Trp53 (KP-mice). Both K and KP mice developed intraepithelial carcinoma of the tongue and had to be killed approximately 2 weeks after induction of K-rasG12D, Trp53 and Ppp6c mutations. Histopathological and transcriptome analyses suggested that Ppp6c deficiency more strongly drove K-rasG12D-initiated tumorigenesis during that period than did Trp53 deficiency. We found that Ppp6c deficiency serves as a driver of KRAS(G12D)-initiated tumorigenesis in mouse tongue.
In Head and neck squamous cell carcinoma (HNSCC) that are HPV(-), EGFR/ERBB2, or EGFR1/3 alterations were most frequent among receptor tyrosine kinases. Kinase targets, such as HRAS, PI3CA, and PTEN, also showed mutations implying perturbed RTK/RAS/PI3K signaling in HNSCC carcinogenesis. Moreover, the tumor suppressor Trp53 was mutant in more than half of the HNSCCs that were HPV(-).
Here, we examined the effect of Ppp6c deficiency on tumorigenesis in mice with tongue-specific expression of K-rasG12D (K-mice) as well as in K-rasG12D mice deficient in Trp53 (KP-mice). Both K and KP mice developed intraepithelial carcinoma of the tongue and had to be killed approximately 2 weeks after induction of K-rasG12D, Trp53 and Ppp6c mutations. Histopathological and transcriptome analyses suggested that Ppp6c deficiency more strongly drove K-rasG12D-initiated tumorigenesis during that period than did Trp53 deficiency. We found that Ppp6c deficiency serves as a driver of KRAS(G12D)-initiated tumorigenesis in mouse tongue.