Renal cell carcinoma (RCC) is asymptomatic at early stages, and thus, initial diagnosis frequently occurs at advanced or even metastatic stages, leading to a high rate of mortality.
Ferric nitrilotriacetate (FeNTA)-induced RCC model is a useful tool to analyze molecular events at different stages of the
carcinogenesis process in vivo. MAPKs' alterations seem to play an important role in the development and maintenance of human RCC
tumors. Based on the above, p38α/β/γ, JNK1/2, and ERK1/2 statuses were studied at early stages of FeNTA-induced renal
carcinogenesis (1 and 2 months of
carcinogen treatment) as well as in
tumor tissue. MAPKs showed distinct response along
carcinogenesis process, either as total
proteins and/or as their phosphorylated forms. While the increase in total and phospho-p38α/β levels became lower as
carcinogenesis progressed, p38γ overexpression grew. Instead, total JNK2 diminished, but JNK1 was elevated at all studied times, and p-JNK1 levels increased at early stages, but not in
tumors. In contrast, p-JNK2 rose at 2 months of treatment and in
tumor tissue. Increased levels of p-ERK1/2 were observed at all stages analyzed. Very interestingly, at 1 and 2 months of FeNTA treatment, no alterations in MAPKs were found in liver or lung, where no primary
tumors are induced with the scheme of FeNTA administration followed here. In conclusion, MAPKs' behavior evolved differentially as renal
carcinogenesis advanced, even among
isoforms of the same family, but it did not change in other tissues. All this strongly suggests a role of these
kinases in FeNTA-induced RCC
tumor development and maintenance.