분화도 좋은 구강 편평상피세포암종에서 Dominant Negative p63 isoform의 발현
EXPRESSION OF DOMINANT NEGATIVE p63 ISOFORM IN WELL-DIFFERENCIATED ORAL SQUAMOUS CELL CARCINOMA
김인수, 김철환, 김경욱,
소속 상세정보
김인수 ( Kim In-Su ) - 단국대학교 치과대학 구강악안면외과학교실
김철환 ( Kim Cheol-Whan ) - 단국대학교 치과대학 구강악안면외과학교실
김경욱 ( Kim Kyung-Wook ) - 단국대학교 치과대학 구강악안면외과학교실
KMID : 0355620070330030191
Abstract
The p53 which is well known as tumor suppressor gene is located at 17p13. p53 is a sequence-specific DNA binding transcription factor that responds to certain cytotoxic stresses, such as DNA damage, by enhancing the transcription of genes that regulate cell-cycle progression as well as programmed cell death. The p63 gene that is located at 3q27-29, is recognized members of the p53 family, and responsible for the transcription of 6 isoforms. Three isoforms (TAp63α, TAp63β, TAp63γ) contain an N-terminal transactivation (TA) domain and can induce apoptosis. The other 3 isoforms (ΔNp63α, ΔNp63β, ΔNp63γ) lack the TA domain and may function in a dominant-negative fashion by inhibiting the transactivation functions of p53 and TAp63 proteins, and thus act as oncoproteins.
A number of studies have investigated the role of p63 in human squamous cell carcinomas from different organs. Only a few studies have examined ΔNp63 isoform in oral squamous cell carcinoma including normal epithelium. This study aimed to evaluate expression of ΔNp63 isoform in human oral squamous cell carcinoma tissue and normal mucosa.
The 3 cases of well differenciated oral squamous cell carcinoma specimen including adjacent normal mucosa were examined, and immunohistochemical study with monoclonal antibody(4A4) and tumor cell apoptosis analysis with Transmission Electon Microscopy were studied. And, RT-PCR analysis was done for expression of ΔNp63 isoform.
The results were as followed.
1. Normal gingiva showed the restricted p63 expression in basal cell layer.
2. Well differentiated squamous cell carcinoma showed mainly p63 expression in overall area of malignancy, especially in basal cell layer to adjacent stromal tissue.
3. Tumor cells around keratinized area with no p63 expression disclosed less micro-organelle in decreased size cytoplasm and severe chromatin margination with nuclear destruction that means apoptosis.
4. Comparison of mRNA expression of ΔNp63 isoform by RT-PCR showed variable expression of ΔNp63 isoform, but ΔNp63αwas most highly expressed in all 3 tumor specimen.
From theses results, it should be suggested that ΔNp63 isoform expression in well differentiated squamous cell carcinoma was closely related to tumor oncogenesis, expecially overexpression of ΔNp63αis a most important factor in tumor genesis of oral squamous cell carcinoma.
키워드
Oral squamous cell carcinoma;p63 gene
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