Induction of the adenoma-carcinoma progression and Cdc25A-B phosphatases by the trefoil factor TFF1 in human colon epithelial cells
- 22 May 2006
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 25 (50), 6628-6636
- https://doi.org/10.1038/sj.onc.1209665
Abstract
TFF1 is overexpressed in inflammatory diseases and human cancers of the digestive and urogenital systems. To examine the transforming potential of TFF1 in human colon epithelial cells, premalignant PC/AA/C1 adenoma cells (PC) derived from a patient with familial adenomatous polyposis (FAP) were transformed by the TFF1 cDNA and used as a model of the adenoma–carcinoma transition. Constitutive expression of TFF1 increased anchorage-independent cell growth in soft agar, and induced or potentiated the growth of colon PC-TFF1 and kidney MDCKts.src-TFF1 tumor xenografts in athymic mice. This resulted in reduction of thapsigargin-induced apoptosis and promotion of collagen type I invasion through several oncogenic pathways. Using the differential display approach to identify TFF1 target genes, we found that the dual specific phosphatases Cdc25A and B implicated in cell cycle transitions are strongly upregulated under active forms in both PC-TFF1 and HCT8/S11-TFF1 colon cancer cells. Accordingly, TFF1 expression is absent in normal human colon crypts but is induced in correlation with Cdc25a and b transcript levels and tumor grade in familial and sporadic colon adenomas and carcinomas. We propose that TFF1 and Cdc25A-B cooperate with other dominant oncogenic pathways to induce the adenoma and adenocarcinoma transitions. Agents that target TFF1/Cdc25 signaling pathways may be useful for treating patients with TFF1-positive solid tumors.Keywords
This publication has 38 references indexed in Scilit:
- Infection with Helicobacter pylori Affects All Major Secretory Cell Populations in the Human AntrumDigestive Diseases and Sciences, 2005
- Trefoil factor family-3 is associated with aggressive behavior of colon cancer cellsClinical & Experimental Metastasis, 2005
- MDM2 Is a Negative Regulator of p21 , Independent of p53Published by Elsevier BV ,2004
- Cyclin A/Cdk2 complexes regulate activation of Cdk1 and Cdc25 phosphatases in human cellsOncogene, 2004
- Cooperativity of p19ARF, Mdm2, and p53 in murine tumorigenesisOncogene, 2003
- Alteration of gene expression during radiation-induced resistance and tumorigenesis in NIH3T3 cells revealed by cDNA microarrays: involvement of MDM2 and CDC25BCarcinogenesis: Integrative Cancer Research, 2003
- Trefoil factors: initiators of mucosal healingNature Reviews Molecular Cell Biology, 2003
- Selective abrogation of the proinvasive activity of the trefoil peptides pS2 and spasmolytic polypeptide by disruption of the EGF receptor signaling pathways in kidney and colonic cancer cellsOncogene, 2003
- The trefoil factor 1 participates in gastrointestinal cell differentiation by delaying G1-S phase transition and reducing apoptosisThe Journal of cell biology, 2002
- Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRC gene.The Journal of cell biology, 1993