Expression of E1AF, an ets-family transcription factor, is correlated with invasive phenotype of oral squamous cell carcinoma

Department of Oral Pathology and Biology, Hokkaido University, Sapporo, Hokkaido, Japan
Oral Oncology (Impact Factor: 3.61). 12/1997; 33(6):426-30. DOI: 10.1016/S0964-1955(97)00047-X
Source: PubMed


E1AF is a newly identified ets-oncogene family transcription factor. Previous reports have noted that E1AF can upregulate promoter activities of several matrix metalloproteinase (MMP) genes and showed that invasive potentials of oral squamous cell carcinoma-derived cell lines are correlated with expression of E1AF and MMPs. The invasive phenotype is restrained by transfection with an antisense E1AF expression vector. Thus, E1AF is thought to be highly correlated with malignant potentials of cancer cells. However, little is known about E1AF expression and cancer cell malignancies in in vivo tumours. In the present study, 27 oral squamous cell carcinoma (SCC) specimens were examined using RT-PCR, Southern blot hybridisation and in situ hybridisation (ISH) and compared to the clinicopathological parameters. Among the 27 patients, E1AF was detected in 15 cases. E1AF mRNA was detected in 13 of 17 invasive SCCs, whereas the majority of SCCs not expressing E1AF showed an expansive growth pattern. Increased prevalence of E1AF-positive oral SCC was observed in cases with nodal metastasis. These results indicate that E1AF may be involved in cancer cell malignancies through its ability to promote invasive potential.

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Available from: Masanobu Shindoh
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    • "Notch is vital for proliferation and cell fate determination [63], whereas PEA3 is critical for cell migration and invasion [64,65]. Both aberrant and unregulated activities can lead to overall malignancy and poor survival [25,40]. "
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    • "These results are consistent with previous findings that demonstrate the involvement of PEA3 group members in proliferation , migration , invasion and in vivo tumor - formation events , particularly in mammary tumor formation ( Habelhah et al . , 1999 ; Hakuma et al . , 2005 ; Hanzawa et al . , 2000 ; Hida et al . , 1997 ; Hiroumi et al . , 2001 ; Kaya et al . , 1996 ; Moss et al . , 2006 ; Shepherd et al . , 2001 ; Upadhyay et al . , 2006 ) . These data also add to the weight of evidence that Pea3 and Erm are tumor - enhancing in mice and highlight a crucial role of these factors in breast - cancer progression . Different genes that are defined as PEA3"
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    • "E1AF mRNA was detected in 15 of the 27, and 13 of 17 E1AF positive SCCs showed invasive phenotype, whereas the majority of SCCs not expressing E1AF showed an expansive growth pattern. Increased prevalence of E1AF-positive oral SCC was observed in cases with nodal metastasis [16]. These results indicate that E1AF may be involved in cancer cell malignancies through its ability to promote invasive potential (Fig. 2). "
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    ABSTRACT: E1AF is an ets-oncogene family transcription factor. E1AF was shown to upregulate multiple matrix metalloproteinase (MMP) genes and contribute to the malignant phenotype of cancer cells by inducing invasive and metastatic activities. E1AF is upregulated by hepatocyte growth factor (HGF) stimulation, which indicates that E1AF would participate in cell motility by HGF/scatter factor. On the other hand, E1AF upregulates p21waf1/cip1 to induce cell cycle arrest when cells are exposed to stress. EWS/ETS fusions are frequently observed in Ewing's sarcoma, and we have revealed that EWS/ETS chimeric protein activates telomerase activity by upregulating hTERT. However, substitution ets binding site (EBS) mutants did not affect the responsiveness to EWS/E1AF. DNA-IP assay showed that the complexes contained EWS/E1AF bound to the hTERT promoter, which suggested that EWS/ETS functions as a co-activator for TERT transcription. Our findings that EWS/ETS acts as a transcriptional co-factor may imply that the transcription pathway is regulated by the interaction of transcription factors.
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