Abstract

Proliferation of the vascular endothelium is one of the early and critical steps of angiogenesis encouraging cellular growth.
The aim of this research proposal is to define the roles of the positive angiogenic factor, called the vascular endothelial growth factor (VEGF) and its co-receptor neuropilin-1 (NRP-1) in the cellular and molecular sequence of events by which estrogens produce tumor angiogenesis in the rat pituitary.
Four specific aims are outlined to attain this objective over a period of three years.
Specific aim 1 will elucidate the impact of estrogens on the expression of VEGF164 and NRP-1 in the pituitaries of different strains of rats and their F1 hybrid progenies by analyzing the genes and protein products.
In specific aim 2 the mechanisms involved in the interaction between estrogen and VEGF164 and NRP-1 at the transcriptional level will be examined.
The third aim will elucidate the role of NRP-1, over expressed in prolactin secreting pituitary tumor cells, on cell survival and angiogenesis.
Specific aim 4 will address the question whether negative regulators like thrombospondin-1 that influence the action of VEGF164 during the development of estrogen induced tumor angiogenesis control the expression of NRP-1.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA087680-03
Application #
6514684
Study Section
Reproductive Endocrinology Study Section (REN)
Program Officer
Sathyamoorthy, Neeraja
Project Start
2000-07-01
Project End
2005-06-30
Budget Start
2002-07-01
Budget End
2005-06-30
Support Year
3
Fiscal Year
2002
Total Cost
$170,100
Indirect Cost

  Institution

Name
University of Kansas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160

  Publications

Kambhampati, Suman; Banerjee, Snigdha; Dhar, Kakali et al. (2010) 2-methoxyestradiol inhibits Barrett's esophageal adenocarcinoma growth and differentiation through differential regulation of the beta-catenin-E-cadherin axis. Mol Cancer Ther 9:523-34
Van Veldhuizen, Peter J; Ray, Gibanananda; Banerjee, Snigdha et al. (2008) 2-Methoxyestradiol modulates beta-catenin in prostate cancer cells: a possible mediator of 2-methoxyestradiol-induced inhibition of cell growth. Int J Cancer 122:567-71
Dhar, Kakali; Banerjee, Snigdha; Dhar, Gopal et al. (2007) Insulin-like growth factor-1 (IGF-1) induces WISP-2/CCN5 via multiple molecular cross-talks and is essential for mitogenic switch by IGF-1 axis in estrogen receptor-positive breast tumor cells. Cancer Res 67:1520-6
Ray, Gibanananda; Dhar, Gopal; Van Veldhuizen, Peter J et al. (2006) Modulation of cell-cycle regulatory signaling network by 2-methoxyestradiol in prostate cancer cells is mediated through multiple signal transduction pathways. Biochemistry 45:3703-13
Islam, Aminul; Banerjee, Swarnali; Kambhampati, Suman et al. (2006) Angiogenic switch in Barrett's adenocarcinoma: the role of vascular endothelial growth factor. Front Biosci 11:2336-48
Sengupta, Krishanu; Banerjee, Snigdha; Dhar, Kakali et al. (2006) WISP-2/CCN5 is involved as a novel signaling intermediate in phorbol ester-protein kinase Calpha-mediated breast tumor cell proliferation. Biochemistry 45:10698-709
Banerjee, Snigdha; Sengupta, Krishanu; Dhar, Kakali et al. (2006) Breast cancer cells secreted platelet-derived growth factor-induced motility of vascular smooth muscle cells is mediated through neuropilin-1. Mol Carcinog 45:871-80
Ray, Gibanananda; Banerjee, Snigdha; Saxena, Neela K et al. (2005) Stimulation of MCF-7 tumor progression in athymic nude mice by 17beta-estradiol induces WISP-2/CCN5 expression in xenografts: a novel signaling molecule in hormonal carcinogenesis. Oncol Rep 13:445-8
Banerjee, Snigdha; Sengupta, Krishanu; Saxena, Neela K et al. (2005) Epidermal growth factor induces WISP-2/CCN5 expression in estrogen receptor-alpha-positive breast tumor cells through multiple molecular cross-talks. Mol Cancer Res 3:151-62
Kambhampati, Suman; Ray, Gibanananda; Sengupta, Krishanu et al. (2005) Growth factors involved in prostate carcinogenesis. Front Biosci 10:1355-67

Showing the most recent 10 out of 18 publications