The objective of this proposal is to examine the role of Insulin-like growth factor II (IGF-II) in the regulation of breast cancer growth. The fundamental hypothesis of this study is that IGF-II is an important and active participant in the process of malignant tumor progression in breast cancer. The insulin-like growth factors, IGF-I and IGF-II, are among the most potent mitogens for breast cancer epithelial cells yet described. Our preliminary data show that IGF-I is expressed in the stroma of normal breast, while IGF-II is expressed in the stroma of breast cancers. Co-culture studies have shown that cultured breast tumor fibroblasts which express IGF-II exert a marked mitogenic stimulus on breast tumor epithelium, and this effect is blocked by inhibiting IGF-II effects. Transfection studies show that induced overexpression of IGF-II in breast tumor epithelial cells confers marked phenotypic changes associated with malignant progression. This proposal will attempt to further define the role of IGF-II in breast cancer, and to test hypotheses aimed at inhibiting breast tumor growth. The goals of this study are: 1) To determine whether IGF-II expression is a prognostic indicator in breast cancer. 2) To examine the mechanism for the transition from IGF-I expression in normal breast stroma to IGF- II expression in breast tumor stroma. 3) To examine whether IGF-I overexpression is associated with the same phenotypic changes of malignant progression as IGF-II. 4) To clarify the role of the IGF-II receptor in IGF-II mediated malignant progression. 5) To attempt to use antisense RNA and oligonucleotides to inhibit IGF-II mediated stromal stimulation of breast cancer growth. 6) To evaluate the role of IGF-II in tumor cell invasion and chemotaxis. It is our hope that these studies will provide a better understanding of the role of IGF-II in breast cancer and help to identify new therapeutic targets for more rational and effective breast cancer treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA058441-02
Application #
2099127
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1993-02-10
Project End
1996-01-31
Budget Start
1994-02-01
Budget End
1995-01-31
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Georgetown University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057