Influence of Smad4-independent pathway of transforming growth factor beta1 on the biological activity of pancreatic cancer cells.
- Author:
Ying CHEN
1
;
Ming-hua ZHU
;
Guan-zhen YU
;
Fang-mei LI
;
Xiao-hong LIU
Author Information
- Publication Type:Journal Article
- MeSH: Cell Line, Tumor; Cell Movement; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; metabolism; Gene Deletion; Genetic Vectors; Humans; Pancreatic Neoplasms; genetics; metabolism; pathology; S Phase; Smad4 Protein; genetics; Transfection; Transforming Growth Factor beta1; biosynthesis; genetics; physiology; Up-Regulation
- From: Chinese Journal of Pathology 2005;34(7):413-416
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study effects of the expression of transforming growth factor (TGF)-beta1 on the growth of Smad4-null pancreatic cancer cells.
METHODSTGF-beta1 eukaryotic expression vector was transfected into pancreatic cancer cell line BxPC3. Effects of the expressison of TGF-beta1 was studied by growth curve analysis and flow cytometry. Cell motility was monitored by wound-healing assay. Western blot was used to estimate the expression level of p21(WAF/CLIP1), a cyclin-dependent kinase inhibitor.
RESULTSTransfection of TGF-beta1 changed the morphology of BxPC3 into spindle shaped cells. The growth rate of BxPC3 began to decrease after the fourth day of TGF-beta1 transfection, compared with the control groups. Flow cytometry showed that the percentages of cells in the S phase were (27.53 +/- 0.02)%, (26.32 +/- 0.01)% and (17.01 +/- 0.03)% in naïve BxPC3, vector-control group and TGF-beta1 transfection group respectively. Lesser cells entered the S phase after TGF-beta1 transfection (P < 0.01), but no difference was seen between the BxPC3 and vector groups (P > 0.05). The expression of p21(WAF/CLIP1) increased upon the expression of TGF-beta1.
CONCLUSIONThe Smad4-independent pathway of TGF-beta1 not only induces epithelial-mesenchymal transition in pancreatic cancer BxPC3, but also inhibits its growth through the up-regulation of p21(WAF/CLIP1).
