In patients with SCCHN, TGF-alpha mRNA was elevated by a mean of 5-fold in 95% of histologically "normal" mucosa samples (P = 0.001) and by a mean of 5-fold in 87.5% of tumors (P = 0.0001) while EGFR mRNA was elevated by a mean of 29-fold in 91% of histologically normal mucosa specimens (P = 0.0005) and by a mean of 69-fold in 92% of tumors (P = 0.0005), compared with mRNA levels in control normal mucosa.
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.
The expression of the c-erbB-2, c-erbB-3 and c-erbB-4 members of the epidermal growth factor receptor family was examined in 16 fresh frozen tissue specimens of SCCHN using avidin-biotin complex immunohistochemistry, with monoclonal and/or polyclonal antibodies directed against each.
We previously demonstrated that biopsy specimens and established cell lines from patients with squamous cell carcinoma of the head and neck (SCCHN) overexpress TGF-alpha and its receptor, epidermal growth factor receptor (EGFR) at both the mRNA and protein levels.
Clones grown at the wild-type temperature (32.5 degreesC) demonstrated a 69% 13% decrease in EGFR mRNA compared with the same cells grown at the mutant temperature (39.5 degreesC; p=0.006) indicating that restoration of wild-type p53 reduces EGFR mRNA levels in this HNSCC cell line.
STAT proteins, including Stat3, are activated by TGF-alpha and EGFR and strategies that downmodulate TGF-alpha or EGFR inhibit SCCHN cell proliferation and abrogate Stat3 activation.
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.
Up-regulation of the epidermal growth factor receptor (EGFR) is critical for the loss of growth control in a variety of human cancers, including squamous cell carcinoma of the head and neck (SCCHN).
Epidermal growth factor receptor (EGFR) is up-regulated and contributes to the loss of growth control in squamous cell carcinoma of the head and neck (SCCHN).
ZD1839 ("Iressa") is an adenosine triphosphate-competitive inhibitor specific to the EGFR tyrosine kinase currently under evaluation as a chemotherapeutic agent in HNSCC.
We have previously shown that antisense gene therapy targeting the epidermal growth factor receptor (EGFR) inhibited tumor growth in a human head and neck squamous cell carcinoma (HNSCC) xenograft model.
Molecular studies of squamous cell carcinoma of the head and neck (HNSCC) have demonstrated multiple genetic abnormalities such as activation of various oncogenes (Ras, Myc, epidermal growth factor receptor, and cyclin D1), tumor suppressor gene inactivation (TP53 and p16), and loss of heterozygosity at numerous chromosomal locations.
Using the same primary tissue samples, increased levels of epidermal growth factor receptor (EGFR) expression were detected in only 32% of tumour tissues, suggesting hPGFS may have the potential to become a drug target or molecular marker for SCCHN.
Clinical evaluation of EGFR-specific monoclonal antibodies and tyrosine kinase inhibitors has demonstrated limited toxicity in SCCHN patients, and concurrent administration with standard cytotoxic therapies has produced additive or synergistic antitumor effects.
These data indicated that in addition to non-small-cell lung cancer, SCCHN harbors the EGFR gene mutations, and suggested the rationale for the clinical applicability of gefinitib to SCCHN patients.
Our previous study revealed that simultaneously targeting epidermal growth factor receptor (EGFR) tyrosine kinase and cyclooxygenase-2 (COX-2) additively or synergistically inhibited growth of squamous cell carcinoma of the head and neck (SCCHN) in vitro.