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Expression and Relation of Beta-Catenin, PTEN Protein and TGF-beta₁ in Squamous Cell Carcinoma and Basal Cell Carcinoma

Author: WuLei
Tutor: LiuLin
School: Zhengzhou University
Course: Surgery
Keywords: Skin tumors β- catenin PTEN protein Transforming growth factor β1
CLC: R739.5
Type: Master's thesis
Year: 2007
Downloads: 140
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Abstract

Background and Purpose cutaneous squamous cell carcinoma (squamous cell carcinoma, SCC) and basal cell carcinoma (basal cell carcinoma, BCC) is the most common types of skin cancer in human beings. However, the mechanism has not yet been fully elucidated. One of the essential characteristics of malignant tumor invasion and metastasis, and tumor cells in order to transfer to the distance from the primary tumor, it must overcome the adhesion between cells. β-catenin (β-catenin, β-cat) as a multifunctional protein complex in the cell membrane and E-cadherin prime (E-cadherin, E-cad) E-cad/cat involved in cell adhesion between the inhibition of tumor cell invasion and metastasis; while gathered in the cytoplasm (nuclear), as the core element mediated Wnt signaling pathway is passed from the extracellular to intracellular promote tumor proliferation and transfer has become a hot present study malignancies mechanism. Chromosome 10 deletion of phosphatase and tensin homolog gene (Phosphatase and homology to tensin homolog deleted on chromosome ten, PTEN) recently discovered a tumor suppressor gene, its encoded protein phosphatase activity, the specific tyrosine residues in protein substrates to phosphorylation, a negative regulator of phosphatidylinositol 3 - kinase (phosphatidylinositol 3-kinase PI3K) / protein kinase B (protein kinase B, PKB) signaling pathway. Studies have pointed out that the PTEN protein can maintain cell membrane β-cat residues dephosphorylated maintained E-cad/cat the stability of the complex, thereby inhibiting tumor cell invasion and metastasis. Transformed growth factor β ₁ (Transforming growth factor-beta ₁, TGF-β ₁), and the role of PTEN protein contrary, can be phosphorylated β- cat's residues, resulting in the free from the cell membrane to the cytoplasm of β-cat. In normal epithelial tissue in a tumor suppressor role in tumor progression, tumor promotion, and the reason is unknown. To investigate the β-cat, PTEN and TGF-β _{in 1} role in the formation and development of the three proteins in the SCC and BCC this topic using immunohistochemistry SP method detected 30 cases of the SCC, 20 cases BCC and 15 cases of the expression of the three proteins in normal skin tissue, and analysis of the relationship between them, and hope to provide a new way of thinking and methods for the prevention and treatment of such diseases. Materials and Methods 30 cases of cutaneous squamous cell carcinoma and 20 cases of basal cell carcinoma of the organization are selected from archived paraffin blocks of Pathology, the First Affiliated Hospital of Zhengzhou University, 2002-2005, drawn parts from the scalp, face, limbs, which 24 males and 26 females, aged 25-88 years of age, an average of 56.22 ± 17.41 years; 25 cases of normal skin tissue from Plastic Surgery, the First Affiliated Hospital of Zhengzhou University, in 2004-2005 non-cancer patients with full-thickness skin graft. According to the WHO classification method, the SCC is divided into three levels, including the grade Ⅰ 22 cases of squamous cell carcinoma, six cases of II-stage squamous cell carcinoma grade III squamous cell carcinoma, 2 cases. Experiments using immunohistochemical SP method, normal skin tissue as a control group, known positive tissue as a positive control (Reagent Company), PBS instead of primary antibody as a negative control. All data applications statistical package SPSS13.0 analysis, α = 0.05 for inspection level, P <0.05 was considered statistically significant. Results 1. β-cat expression in SCC and BCC: β-cat in normal skin tissue mainly located in the cell membrane, the the SCC cell membrane expression of a large number of abnormal accumulation missing replace them with the cytoplasm (nuclear). SCC in the membrane of the β-cat expression miss rate and ectopic expression were higher than normal skin, but pathological grading of tumor cells without significant correlation (P = 0.638> 0.050); membrane expression decreased BCC but not obvious disappeared, at the same time the cytoplasm nucleus a large number of metachromatic. BCC β-cat abnormal expression rate was 70.00% (14/20) than in normal skin tissue abnormal expression rate of 12.00% (3/25) (P = 0.000 <0.050), but the membrane expression rate was no significant difference . Two cancer tissue abnormal expression of β-cat no significant difference (P = 0.599> 0.050). 2. PTEN protein expression in the SCG and BCC: PTEN protein expression is mainly localized in the cytoplasm. SCC in most PTEN protein expression is missing, the positive expression rate was only 30.00% (9/30), much lower than the normal skin tissue in 92.00% (23/25) and 60.00% (12/20) of the BCC positive expression rate ( P = 0.000 <0.050, P = 0.035 <0.050), but the degree of differentiation of the tumor cells had no significant correlation (P = 0.215> 0.050); BCC of PTEN protein expression was lower than that of normal skin, the difference was statistically significant ( P = 0.027 <0.050). 3. TGF-β ₁ expression in SCC and BCC: TGF-β ₁ positive expression in the cytoplasm. Significant TGF-β ₁ high positive expression in the SCC, the positive rate was 73.33% (22/30), significantly higher than 24.00% of the BCC, 45.00% (9/20) and normal skin ( TGF-β positive expression rate of 6/25) (respectively, P = 0.043 <0.050, P = 0.000 <0.050), while no significant correlation with tumor grade (P = 1.000> 0.050); normal skin tissue ₁ positive expression rate of BCC compared the difference was not statistically significant (P = 0.138> 0.050). 4. Correlation analysis: β-cat in the SCC and BCC normal expression of PTEN protein expression was positively correlated (P = 0.003 <0.050, r = 0.419), and TGF-β ₁ positive expression There was a negative correlation (P = 0.018 <0.050, r = -0.381). PTEN protein positive expression and TGF-β ₁ positive expression was negatively correlated (r = -0.503, P = 0.000 <0.050). Conclusion 1. β-cat in the SCC, the apparent lack of membrane expression and ectopic expression, suggesting that cell adhesion function caused by abnormal expression of β-cat damage and abnormal activation of the Wnt signaling pathway in SCC incidence of the development process may play an important role in . But there is no obvious relationship with SCC differentiation. 2. obvious ectopic expression of β-cat in BCC is not obvious, but the film expressing deletion prompt abnormal activation of Wnt signaling may be involved in the formation process of the BCC. Mediated adhesion function of β-cat undermine with BCC a relationship is not obvious. 3. SCC in recurrent deletion of PTEN protein expression and TGF-β ₁ abnormally high expression may be one of the formation mechanism of the SCC, SCC differentiation. 4. The SCC loss of expression of PTEN protein and TGF-β ₁ abnormally high expression together to promote the abnormal expression of β-cat cells, and thus lead to homogeneity adhesion between tumor cells destruction and abnormal activation of the Wnt signaling pathway, ultimately leading to tumor proliferation and metastasis ability.

Expression and Relation of Beta-Catenin, PTEN Protein and TGF-beta1 in Squamous Cell Carcinoma and Basal Cell Carcinoma

Abstract

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Expression and Relation of Beta-Catenin, PTEN Protein and TGF-beta₁ in Squamous Cell Carcinoma and Basal Cell Carcinoma