Abstract

The long term goal of this study is to determine the role of TGFbeta RII receptor (RII) in pancreatic cancer. Loss of response to TGFbeta appears common to pancreatic cancer, which is often caused by a loss of the RII gene expression. The hypothesis to be tested in this revised application is that the loss of RII expression is caused by ras-mediated down regulation of the gene and that lack of a functional RII receptor plays an important role in the tumorigenic properties of pancreatic cancers.
The specific aims are 1) Determine the mechanism by which oncogenic ras inhibits RII expression and/or causes resistance to growth inhibition by TGFbeta, and 2) Determine the biological role of RII in tumor progression in ras-mutated pancreatic cancer cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA069122-05
Application #
6172812
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Freeman, Colette S
Project Start
1997-08-01
Project End
2002-08-31
Budget Start
2000-06-01
Budget End
2002-08-31
Support Year
5
Fiscal Year
2000
Total Cost
$224,431
Indirect Cost

  Institution

Name
University of Texas Health Science Center San Antonio
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229

  Publications

Zhao, Shujie; Chen, Chen; Chang, Katherine et al. (2016) CD44 Expression Level and Isoform Contributes to Pancreatic Cancer Cell Plasticity, Invasiveness, and Response to Therapy. Clin Cancer Res 22:5592-5604
Chang, Katherine; Karnad, Anand; Zhao, Shujie et al. (2015) Roles of c-Met and RON kinases in tumor progression and their potential as therapeutic targets. Oncotarget 6:3507-18
Gong, Jingjing; Xie, Jianping; Bedolla, Roble et al. (2014) Combined targeting of STAT3/NF-?B/COX-2/EP4 for effective management of pancreatic cancer. Clin Cancer Res 20:1259-73
Bera, Alakesh; VenkataSubbaRao, Kolaparthi; Manoharan, Muthu Saravanan et al. (2014) A miRNA signature of chemoresistant mesenchymal phenotype identifies novel molecular targets associated with advanced pancreatic cancer. PLoS One 9:e106343
Zhao, S; Cao, L; Freeman, J W (2013) Knockdown of RON receptor kinase delays but does not prevent tumor progression while enhancing HGF/MET signaling in pancreatic cancer cell lines. Oncogenesis 2:e76
Bera, Alakesh; Zhao, Shujie; Cao, Lin et al. (2013) Oncogenic K-Ras and loss of Smad4 mediate invasion by activating an EGFR/NF-?B Axis that induces expression of MMP9 and uPA in human pancreas progenitor cells. PLoS One 8:e82282
Venkatasubbarao, Kolaparthi; Peterson, Lindsay; Zhao, Shujie et al. (2013) Inhibiting signal transducer and activator of transcription-3 increases response to gemcitabine and delays progression of pancreatic cancer. Mol Cancer 12:104
Thangasamy, Amalraj; Rogge, Jessica; Krishnegowda, Naveen K et al. (2011) Novel function of transcription factor Nrf2 as an inhibitor of RON tyrosine kinase receptor-mediated cancer cell invasion. J Biol Chem 286:32115-22
Zhao, Shujie; Wang, Yubao; Cao, Lin et al. (2010) Expression of oncogenic K-ras and loss of Smad4 cooperate to induce the expression of EGFR and to promote invasion of immortalized human pancreas ductal cells. Int J Cancer 127:2076-87
Zhao, Shujie; Venkatasubbarao, Kolaparthi; Lazor, Jillian W et al. (2008) Inhibition of STAT3 Tyr705 phosphorylation by Smad4 suppresses transforming growth factor beta-mediated invasion and metastasis in pancreatic cancer cells. Cancer Res 68:4221-8

Showing the most recent 10 out of 15 publications