PMID- 15887216 OWN - NLM STAT- MEDLINE DCOM- 20051101 LR - 20151119 IS - 1043-3074 (Print) IS - 1043-3074 (Linking) VI - 27 IP - 7 DP - 2005 Jul TI - Expression of ets-1 transcription factor in human head and neck squamous cell carcinoma and effect of histamine on metastatic potential of invasive tumor through the regulation of expression of ets-1 and matrix metalloproteinase-3. PG - 585-96 AB - BACKGROUND: Ets-1 controls the expression of critical genes involved in matrix remodeling. The matrix metalloproteinase-3 (MMP-3) and urokinase type plasminogen activator (uPA) are typical ets-1 responsive genes. Recent studies have shown an increase in histamine synthesis and content in various human neoplasias. We hypothesized that the increased local histamine overproduction contributed to activation of matrix remodeling through the activation of MMP-3 expression of peritumoral fibroblasts by means of ets-1 regulation in head and neck squamous cell carcinomas (HNSCCs). METHODS: Paraffin-embedded sections of 30 HNSCCs were immunostained for ets-1. The presence of ets-1 and MMP-3 mRNA in tumor samples was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR). To simulate stromal reaction in vitro, cultured human mucosal fibroblast was used. The level of ets-1 and MMP-3 mRNA was compared by use of RT-PCR, as was their protein with flow-cytometry, in the presence or absence of basic fibroblast growth factor (bFGF) (10 ng/mL) and histamine (1 microM). RESULTS: Correlation between ets-1 expression and clinicopathologic background was not significant. In all cases, expression of ets-1 was seen in the stroma. In in vitro study, histamine upregulates production of ets-1 and MMP-3 in cultured fibroblast, and bFGF can stimulate histamine expression in fibroblast. Immunofluorescence staining supported the results of RT-PCR and flow cytometry. CONCLUSIONS: Ets-1 expression in HNSCCs has no prognostic value; however, ets-1 plays an important role in tumor-host interaction. Histamine may accelerate the spread of HNSCC through an ets-1-related mechanism. FAU - Horvath, Barnabas AU - Horvath B AD - Department of Ear, Nose and Throat Diseases, National Medical Center 1135, Szabolcs u. 35, Budapest, Hungary. bhorvath@ogyik.hu FAU - Hegyesi, Hargita AU - Hegyesi H FAU - Nagy, Pal AU - Nagy P FAU - Falus, Andras AU - Falus A FAU - Schaff, Zsuzsa AU - Schaff Z LA - eng PT - Journal Article PL - United States TA - Head Neck JT - Head & neck JID - 8902541 RN - 0 (Biomarkers, Tumor) RN - 0 (ETS1 protein, human) RN - 0 (Proto-Oncogene Protein c-ets-1) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Proto-Oncogene Proteins c-ets) RN - 0 (Transcription Factors) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 820484N8I3 (Histamine) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Biomarkers, Tumor/genetics/metabolism MH - Carcinoma, Squamous Cell/genetics/*metabolism/secondary MH - Cell Culture Techniques MH - Female MH - Fibroblast Growth Factor 2/metabolism MH - Flow Cytometry MH - Head and Neck Neoplasms/genetics/*metabolism/pathology MH - Histamine/*pharmacology MH - Humans MH - Immunohistochemistry MH - Male MH - Matrix Metalloproteinase 3/genetics/*metabolism MH - Neoplasm Invasiveness MH - Proto-Oncogene Protein c-ets-1 MH - Proto-Oncogene Proteins/genetics/*metabolism MH - Proto-Oncogene Proteins c-ets MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transcription Factors/genetics/*metabolism MH - Up-Regulation/drug effects EDAT- 2005/05/12 09:00 MHDA- 2005/11/03 09:00 CRDT- 2005/05/12 09:00 PHST- 2005/05/12 09:00 [pubmed] PHST- 2005/11/03 09:00 [medline] PHST- 2005/05/12 09:00 [entrez] AID - 10.1002/hed.20188 [doi] PST - ppublish SO - Head Neck. 2005 Jul;27(7):585-96. doi: 10.1002/hed.20188.