Objective To study the relation between expressions of transforming growth factor β1 （TGF-β1）, transforming growth factor receptor type Ⅰ (TβRⅠ) and cell proliferation, cell cycle in gallbladder carcinomas, to disclose the mechanism of TGF-β1 and TβRⅠin the gallbladder carcinogenesis，and to evaluate their values in the prognosis of gallbladder carcinomas.
Methods Thirty five gallbladder carcinomas 〔age （57.94± 4.61） years, 14 male cases and 21 female cases〕 comprised 32 adenocarcinomas, 2 adenosquamous carcinoma and 1 squamous cell carcinomas. Formalin fixed, paraffin embedded sections from gallbladder carcinomas were immunostained with TGF-β1, TβRⅠ, PCNA, cyclin E antibodies by immunochemical assays. Gallbladder adenoma and chronic cholecystitis were collected as non-malignant controls. Patients of gallbladder carcinomas were followed up.
Results Positive immunostaining rate of TGF-β1 was 57.14% in gallbladder carcinomas, which was significantly higher than that in gallbladder adenomas and chronic cholecystitis (P＜0.01, respectively). Expression of TGF-β1 was associated with Nevin stage, lymph nodes and distant metastasis (P＜0.05, P＜0.01, respectively). Expression of TGF-β1 was positively correlated with expression of PCNA LI and cyclin E (r=0.523 2, P=0.001 3; r=0.406 5, P=0.015 4), and 34.29% of gallbladder carcinomas were immunostained positively for TβRⅠ. Expression of TβRⅠwas significantly lower in gallbladder carcinomas than that in gallbladder adenomas and cholecystitis (P＜0.05, respectively). It was significantly lower in gallbladder carcinomas patients with lymph nodes and distant metastases than in those without (P＜0.05). Expression of TβRⅠwas negatively correlated with PCNA LI (r=-0.402 4, P=0.016 6). Patients with negative expression of TGF-β1 and/or positive expression of TβRⅠ had significant longer survival rates than those with positive expression of TGF-β1 and/or negative expression of TβRⅠ(P＜0.01, P＜0.05, respectively). Expressions of TGF-β1 and TβRⅠ correlated with prognosis of gallbladder carcinomas closely.
Conclusion TGF-β1 and TβRⅠ have close correlation with cell proliferation, cell cycle of gallbladder carcinomas and are important biological markers of carcinogenesis and progress of gallbladder carcinomas. The escape of growth inhibition of TGF-β1 due to low expression of TβRⅠand carcinogenesis of TGF-β1 may play an important role in gallbladder carcinogenesis. TGF-β1 and TβRⅠare valuable indices for judging the prognosis of gallbladder carcinoma.
Citation：
ZHU Yaqing,CHEN Shuzhou,CHEN Yuquan,WANG Xuehao.. Effects on TGF-β1 and TβRⅠ in Carcinogenesis and Prognosis of Gallbladder Carcinomas. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2007, 14(4): 448-452. doi:
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| 1. |
6 Perez-Gomez E, Eleno N, Lopez-Novoa JM, et al. Characterization of murine S-endoglinisoform and its effects on tumor development [Ｊ] . Oncogene, 2005; 24(27)∶4450
7 Tsushima H, Ito N, Tamura S, et al. Circulating transforming growth factor beta 1 as a predictor of liver metastasis after resection in colorectal cancer [Ｊ] . Clin Cancer Res, 2001; 7(5)∶1258.
|
| 2. |
Roberts AB, Wakefield LM. The two faces of transforming growth factor beta in carcinogenesis [Ｊ] . Proc Natl Acad Sci USA， 2003; 100(15)∶8621.
|
| 3. |
Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling [Ｊ] . Nature， 2003; 425(6958)∶577.
|
| 4. |
Weeks BH, He W, Olson KL, et al. Inducible expression of transforming growth factor beta 1 in papillomas causes rapid metastasis [Ｊ] . Cancer Res， 2001; 61(20)∶7435.
|
| 5. |
Han G, Lu SL, Li AG, et al. Distinct mechanisms of TGF-beta1-mediated epithelial-to-mesenchymal transition and metastasis during skin carcinogenesis [Ｊ] . J Clin Invest， 2005; 115(7)∶1714 .
|
| 6. |
Fischer AN, Herrera B, Mikula M, et al. Integration of Ras subeffector signaling in TGF-beta mediated late stage hepatocarcinogenesis [Ｊ] . Carcinogenesis, 2005; 26(5)∶931.
|
| 7. |
Kitamura K, Kasuya K, Tsuchida A, et al. Immunohistochemical analysis of transforming growth factor beta in gallbladder cancer [Ｊ] . Oncol Rep, 2003; 10(2)∶327.
|
| 8. |
Fukai Y, Fukuchi M, Masuda N, et al. Reduced expression of transforming growth factor-beta receptors is an unfavorable prognostic factor in human esophageal squamous cell carcinoma [Ｊ] . Int J Cancer, 2003; 104(2)∶161.
|
| 9. |
Miyajima A, Asano T, Seta K, et al. Loss of expression of transforming growth factor-beta receptor as a prognostic factor in patients with renal cell carcinoma [Ｊ] . Urology, 2003; 61(5)∶1072 .
|
| 10. |
Tokunaga H, Lee DH, Kim IY, et al. Decreased expression of transforming growth factor beta receptor type Ⅰ is associated with poor prognosis in bladder transitional cell carcinoma patients [Ｊ] . Clin Cancer Res, 1999; 5(9)∶2520.
|
| 11. |
Maga G, Hubscher U. Proliferating cell nuclear antigen (PCNA): a dancer with many partners [Ｊ] . J Cell Sci, 2003; 116(Pt 15)∶3051.
|
| 12. |
Kannouche PL, Lehmann AR. Ubiquitination of PCNA and the polymerase switch in human cells [Ｊ] . Cell Cycle, 2004; 3(8)∶1011.
|
| 13. |
Hwang HC, Clurman BE. Cyclin E in normal and neoplastic cell cycles [Ｊ] . Oncogene, 2005; 24(17)∶2776.
|
| 14. |
Musgrove EA. Cyclins: roles in mitogenic signaling and oncogenic transformation [Ｊ] . Growth Factors, 2006; 24(1)∶13.
|
| 15. |
周彦明， 李玉民， 朱有全， 等. cyclin E和p27kip1蛋白在胆囊癌组织中的表达及其意义 [Ｊ] . 中国普外基础与临床杂志， 2004； 11（2）∶148.
|
- 1. 6 Perez-Gomez E, Eleno N, Lopez-Novoa JM, et al. Characterization of murine S-endoglinisoform and its effects on tumor development [Ｊ] . Oncogene, 2005; 24(27)∶4450
7 Tsushima H, Ito N, Tamura S, et al. Circulating transforming growth factor beta 1 as a predictor of liver metastasis after resection in colorectal cancer [Ｊ] . Clin Cancer Res, 2001; 7(5)∶1258.
- 2. Roberts AB, Wakefield LM. The two faces of transforming growth factor beta in carcinogenesis [Ｊ] . Proc Natl Acad Sci USA， 2003; 100(15)∶8621.
- 3. Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling [Ｊ] . Nature， 2003; 425(6958)∶577.
- 4. Weeks BH, He W, Olson KL, et al. Inducible expression of transforming growth factor beta 1 in papillomas causes rapid metastasis [Ｊ] . Cancer Res， 2001; 61(20)∶7435.
- 5. Han G, Lu SL, Li AG, et al. Distinct mechanisms of TGF-beta1-mediated epithelial-to-mesenchymal transition and metastasis during skin carcinogenesis [Ｊ] . J Clin Invest， 2005; 115(7)∶1714 .
- 6. Fischer AN, Herrera B, Mikula M, et al. Integration of Ras subeffector signaling in TGF-beta mediated late stage hepatocarcinogenesis [Ｊ] . Carcinogenesis, 2005; 26(5)∶931.
- 7. Kitamura K, Kasuya K, Tsuchida A, et al. Immunohistochemical analysis of transforming growth factor beta in gallbladder cancer [Ｊ] . Oncol Rep, 2003; 10(2)∶327.
- 8. Fukai Y, Fukuchi M, Masuda N, et al. Reduced expression of transforming growth factor-beta receptors is an unfavorable prognostic factor in human esophageal squamous cell carcinoma [Ｊ] . Int J Cancer, 2003; 104(2)∶161.
- 9. Miyajima A, Asano T, Seta K, et al. Loss of expression of transforming growth factor-beta receptor as a prognostic factor in patients with renal cell carcinoma [Ｊ] . Urology, 2003; 61(5)∶1072 .
- 10. Tokunaga H, Lee DH, Kim IY, et al. Decreased expression of transforming growth factor beta receptor type Ⅰ is associated with poor prognosis in bladder transitional cell carcinoma patients [Ｊ] . Clin Cancer Res, 1999; 5(9)∶2520.
- 11. Maga G, Hubscher U. Proliferating cell nuclear antigen (PCNA): a dancer with many partners [Ｊ] . J Cell Sci, 2003; 116(Pt 15)∶3051.
- 12. Kannouche PL, Lehmann AR. Ubiquitination of PCNA and the polymerase switch in human cells [Ｊ] . Cell Cycle, 2004; 3(8)∶1011.
- 13. Hwang HC, Clurman BE. Cyclin E in normal and neoplastic cell cycles [Ｊ] . Oncogene, 2005; 24(17)∶2776.
- 14. Musgrove EA. Cyclins: roles in mitogenic signaling and oncogenic transformation [Ｊ] . Growth Factors, 2006; 24(1)∶13.
- 15. 周彦明， 李玉民， 朱有全， 等. cyclin E和p27kip1蛋白在胆囊癌组织中的表达及其意义 [Ｊ] . 中国普外基础与临床杂志， 2004； 11（2）∶148.
