The long-term objective of this research proposal is to identify the mechanisms that induce metastatic dormancy and their subsequent chemo-resistance.
Specific Aims : (1) To determine the functional contribution of PERK-dependent signaling pathways to p38-dependent induction of tumor dormancy in vivo; (2) To identify the molecular mechanisms that couple upregulation of BiP and activation of PERK to survival and drug resistance of dormant carcinoma cells. Tumorigenic (T-HEp3) and dormant (D-HEp3) cell-lines derived from HEp3 human squamous carcinoma will be used in chicken embryo chorioallantoic membrane (CAM) and nude mouse in vivo model systems. Stable and transient expression systems will be used to specifically modulate the PERK signaling and BiP expression, to determine if this pathway induces or interrupts dormancy and drug resistance in T- and D-HEp3 cells respectively. These studies will contribute to (1) understanding the mechanisms that regulate cancer dormancy and drug-resistance and (2) combine novel drugs that inhibit dormant tumor cell survival with conventional chemotherapeutics to eradicate residual cancer disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA117621-02
Application #
7105017
Study Section
Special Emphasis Panel (ZRG1-F09 (20))
Program Officer
Lohrey, Nancy
Project Start
2005-07-15
Project End
2008-07-14
Budget Start
2006-07-15
Budget End
2007-07-14
Support Year
2
Fiscal Year
2006
Total Cost
$50,428
Indirect Cost
Name
State University of New York at Albany
Department
Other Basic Sciences
Type
Schools of Public Health
DUNS #
152652822
City
Albany
State
NY
Country
United States
Zip Code
12222
Ranganathan, Aparna C; Ojha, Shishir; Kourtidis, Antonis et al. (2008) Dual function of pancreatic endoplasmic reticulum kinase in tumor cell growth arrest and survival. Cancer Res 68:3260-8