To investigate the role of PTEN loss of expression in head and neck squamous cell carcinoma (HNSCC) response to cetuximab, we used siRNA in Cal 27 cells and then evaluated key signaling protein activation (pAKT and pERK 1/2) as well as cell viability and proliferation.
The most common abnormalities downstream from EGFR in HNSCC are in the PI3K pathway, activated via loss of expression of the regulator PTEN, or via PI3K mutation.
We hypothesize that the loss of PTEN expression as well as the subcellular localization could be of interest as a predictive marker of recurrence in HNSCC.
Our results suggest that nAChRs might exert their function through pathways different from PI3-K/Akt/PTEN and that alpha3, alpha5 or alpha7 nAChR subunit expression might not be useful prognostic markers in HNSCC.
Overall, our study highlights the likely clinical relevance of reduced PTEN expression and/or inactivation in HNSCC progression, while the combined Pten deletion with exposure to tobacco carcinogens or their surrogates may provide a unique experimental model system to study novel molecular targeted treatments for HNSCC patients.
We conclude from this study that overexpression of E2F-1 and p53 can reverse telomerase activity in SCCHN cell lines and that telomerase activity may be involved in cancer cell immortalization.
Head and neck squamous cell carcinoma (HNSCC) and many other epithelial malignancies exhibit increased proliferation, invasion, and inflammation, concomitant with aberrant nuclear activation of TP53 and NF-κB family members ΔNp63, cRel, and RelA.
These studies suggest that EGFR-targeting tracers can be used to monitor EGFR receptor expression in HNSCC and have the potential to noninvasively monitor cetuximab treatment and steer individualized treatment regimens.
We have previously demonstrated that RA down-modulates transforming growth factor (TGF)-alpha and epidermal growth factor receptor (EGFR) levels in head and neck squamous cell carcinoma by decreasing the transcription rate of these two genes.
Mechanistic studies reveal that attenuated HNSCC cell growth in response to DEK loss was associated with reduced expression of the oncogenic p53 family member, ΔNp63.
These experiments indicate that EGFR gene expression and function is critical for SCCHN cell growth but not for growth of normal mucosa cells and therefore may serve as a tumor-specific target for preventive and therapeutic strategies in head and neck cancer.