Expression of TGF-beta1, TbetaRII and Smad4 in colorectal carcinoma.
BACKGROUND
Many colorectal carcinomas are resistant to the growth inhibitory response of transforming growth factor-beta (TGF-beta) due to alterations of components along the TGF-beta signaling pathway. The aim of this study was to examine the expression of TGF-beta1, TbetaRII and Smad4 in human colorectal carcinoma and their relationships with cancer growth.


METHODS
Immunohistochemistry and in situ hybridization were performed in 38 cases of colorectal carcinoma.


RESULTS
Intense signal for TGF-beta1 protein and TGF-beta1 mRNA were found in 71.1% (27/38) and 77.8% (21/27) of colorectal carcinoma, respectively. Intensive TbetaRII mRNA were detected only in 40% (11/27) cancer tissues (p<0.05). 65.8% (25/38) of colorectal carcinoma displayed decreased expression in TbetaRII immunoreactivity staining (p<0.05). Smad4 protein and Smad4 mRNA were reduced in 63.2% (24/38) and 63% (17/27) of tumors, respectively. Smad4 expression was related to tumor differentiation and Duke's stage (p<0.05). Furthermore, TGF-beta1-positive tumors with lymph node metastasis preferentially had significant reduced Smad4 expression (p<0.05).


CONCLUSIONS
Down-regulation of TbetaRII as well as the over-expression of TGF-beta1 play a possible role for the escape of colorectal carcinoma from TGF-beta-mediated growth inhibition. Reduced Smad4 is associated with malignancy and progression of colorectal carcinoma.
Xu
Wei-Qing
WQ
Department of Pathology, Shanghai Jiao Tong University School of Medicine, 227 South Chong Qing Rd. Shanghai, 200025, People's Republic of China.
Jiang
Xu-Cheng
XC
Zheng
Lin
L
Yu
Yin-Yan
YY
Tang
Jian-Min
JM
D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009362:Neoplasm Metastasis / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D051901:Smad4 Protein / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D053773:Transforming Growth Factor beta1