Selective reduction of extracellular signal-regulated protein kinase (ERK) phosphorylation in squamous cell carcinoma of the larynx

Abstract

Mitogen-activated protein kinase (MAPK) cascades transmit and amplify signals involved in cell proliferation as well as in cell death. In this study, the potential derangement of MAPK pathways has been evaluated in human squamous cell carcinomas (SCC) of the larynx. The expression and activity of the MAPK p38, ERK1/2 p44/p42 and JNK/SAPK p46/p54 have been investigated by immunoblot analysis of tissue homogenates in 27 samples of primary laryngeal cancer and in 27 paired non-neoplastic laryngeal mucosa. On the same tissues, the activation of MAPK JNK/SAPK p46/p54 was also analyzed by an ELISA assay. The results obtained showed that both total and phosphorylated levels of JNK/SAPK p46/p54 and p38 were not different between tumor and normal samples. Conversely, while total protein levels for both ERK1 p44 and ERK2 p42 were not statistically different between tumor and normal samples, the analysis of the level of the activated forms of ERK1/2 showed a statistically significant decreased phosphorylation of both isoforms in the tumor samples compared to the control tissues. The rate of reduction was similar for both isoforms. Immunohistochemical analysis of all the activated MAPK (p38, JNK/SAPK p46/p54 and ERK1/2 p44/p42 ) in both laryngeal SCC and normal mucosa demonstrated no difference of cellular localization. Activated ERK1/2 p44/p42 and activated p38 demonstrated a nucleo-cytoplasmic distribution whereas activated JNK/SAPK p46/p54 were localized into the cytoplasmic membrane. The decreased activity of ERK1/2 p44/42 in laryngeal SCC might reflect alterations in tumor suppressing activity or might derive from the interplay among various transduction pathways.

Roles of phosphorylated JNK in esophageal squamous cell carcinomas of kazakh ethnic

“…So far, there have been little report documenting that p‐JNK expression and its possible roles in clinical tumor specimens, there have been however several literatures reporting that simultaneous evaluation of p‐JNK together with phosphorylated forms of the other two members of MAPKs family, p‐p38 and p‐ERK in the same specimens. In one previous study, Garavello et al not only detected p‐ERK and p‐p38 using Western blotting and IHC but also evaluated p‐JNK expression using ELISA assay in 27 paired squamous cell carcinoma of the larynx and corresponding normal controls, there was no statistically significant differences of p‐JNK expression between tumor and normal laryngeal samples. Similarly, Aguzzi et al also simultaneously evaluated p‐ERK, p‐p38, and p‐JNK in 30 tissue samples of squamous cell carcinoma of the oral cavity and their paired nonneoplastic controls.…”

Association between metalloproteinases 2 and 9 activity and ERK1/2 phosphorylation status in head and neck cancers: An ex vivo study

“…After activation ERK1/2 can phosphorylate and activate different downstream targets, either citoplasmatic or nuclear, including cytoskeletal proteins and transcription factors such as AP-1, c-Fos and Elk-1 (15). According to this complex role in determining either proliferation or cell death, aberrant activation of ERK pathway is frequently seen in cancers (16)(17)(18).…”