Overexpression of Fos‐related antigen‐1 in head and neck squamous cell carcinoma

Abstract

The activating protein-1 (AP-1) family of transcription factors has been implicated in the control of proliferation and differentiation of keratinocytes, but its role in malignant transformation is not clear. The aim of this study is to assess the pattern of mRNA expression of jun-fos AP-1 family members in 45 samples of head and neck squamous cell carcinomas (HNSCC) and matched adjacent mucosa by means of Northern blot analysis. Transcripts of all family members were identified, except for JunB that was detected only by means of reverse transcription polymerase chain reaction. Neither c-Fos nor JunD or FosB mRNA differed between tumours and normal tissues. We observed a strong Fos-related antigen-1 (Fra-1) and Fra-2 expression, but only Fra-1 mRNA densitometric values were higher in tumour, compared to normal adjacent mucosa (t-test, P = 0.006). A direct relationship between the positive expression of Fra-1 mRNA, above tumour median, was associated with the presence of compromised lymph nodes (Fischer exact test, P = 0.006). In addition, Fra-1 protein staining was assessed in a collection of 180 tumours and 29 histologically normal samples adjacent to tumours in a tissue array. Weak reactivity, restricted to the basal cell layer, was detected in 79% of tumour adjacent normal tissues, opposed to the intense reactivity of cancer tissues. In the subgroup of oral cancers, we have observed a shift in Fra-1 immunoreactivity, as long as the number of patients in each category, cytoplasmic or nuclear/cytoplasmic staining, was analysed (Fischer exact test, P = 0.0005). Thus, Fra-1 gene induction and accumulation of Fra-1 protein may contribute to the neoplastic phenotype in HNSCC.

FRA-1 Proto-Oncogene Induces Lung Epithelial Cell Invasion and Anchorage-Independent Growth In vitro, but Is Insufficient to Promote Tumor Growth In vivo

“…The expression of FRA-1 is persistently induced in bronchial epithelial cells by lung carcinogens such as tobacco smoke (9), tumor-promoting phorbol esters, and mitogens (10,11). Consistent with these observations, overexpression of FRA-1 has been noted in squamous cell carcinomas of the head and neck (12), esophagus, and stomach (13). The transition from the small cell to the nonsmall cell lung cancer (NSCLC) phenotype induced by the H-ras/ c-myc oncogenes is accompanied by specific induction of FRA-1, suggesting a prominent role for this transcription factor in maintaining NSCLCs in a differentiated state (14).…”

C-fos Assessment as a Marker of Anti–Epidermal Growth Factor Receptor Effect

“…However, as we do not have sequential samples of untreated patients, we cannot define the natural evolution of c-fos levels in patient tumors and whether this effect may be related to gefitinib treatment. Interestingly c-fos levels have been found to be similar between normal and tumor tissue in head and neck squamous cell carcinoma patient samples (12), but significantly higher in tumor tissue in esophageal cancer patients (13).…”

Effects of Expression of Transcriptional Factor AP-1 FOSL1 Gene on Psoriatic Process

“…The role FOSL1 as a proto-oncogene is now actively studied [4,5,8,10,11]. The main role of FOSL1 gene is determined by its overexpression in various cell lines and clinical samples (epithelial cancer cells).…”