Estrogen-dependent initiation or promotion of breast carcinoma growth is believed to have a basis in hyper-proliferation of estrogen-responsive cells. However, proliferation substrate and adjacent cells, an event that is required for cell movement and dissemination into surrounding tissue. the estrogen-dependence of some breast tumor development and growth suggest a role for this steroid in regulation of tumor cell-matrix and cell-cell adhesions. The MCF-7 mammary carcinoma cell line is frequently used as an in vitro model to study hormonal control of breast cancer. In response to 17-B-estradiol MCF-7 human mammary carcinoma cells undergo a loss of cell-matrix adhesion plaque proteins and a change in the composition of cell-cell adhesions. Talin- and vinculin-rich cell-matrix adhesions are diminished in monolayers of confluent and post confluent cultures. Vinculin is not cadherin, is markedly reduced. Parallel to the changes in cell-matrix and cell-cell adhesions, prominent F-actin-rich cytoplasmic structures develop from the ventral surface of individuals cells. The actin-rich structures resemble, but are distinctly different from, lamellipodia. Plakoglobin, a cell-cell cytoplasmic adhesion plaque protein, accumulates throughout the ventral region of cell monolayers and co-distributes with the F-actin structures. A cadherin-related antigen also accumulates beneath treated monolayers. The matrix adhesions that mediate monolayers attachment to the substrate, to an atypical adhesion consisting of components normally found in cell- cell adhesions. The reduced substrate and detachment of responsive carcinoma cells from underlying matrix and adjacent cells to become freely motile. The newly acquired ventral surface adhesions may function in adhesions to, migration on, and invasion of surrounding cells. The proposed study will examine the alterations in intergin receptor expression parallel that if talin and vinculin. The study will also examine the nature of the newly, acquired ventral surface adhesion and determine if it functions in cell adhesion, migration, and invasion in vitro.
The specific aims of this application are to: 1) directly determine if the spatial and temporal expression of integrin alpha5, alphav, Beta1, and Beta3 subunits is altered in relation to cell- matrix adhesions in response to estradiol; 2) determine the exact spatial relationship of plakoglobin, alpha- catenin, N-cadherin, and E-cadherin to the F-actin-rich ventral surface structures; 3) determine if the F-actin-rich structures function in adhesion to, migration on, and invasion of endothelial cell monolayers known to express surface cadherins.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA063542-04
Application #
2414319
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1994-05-01
Project End
1999-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Wadsworth Center
Department
Type
DUNS #
110521739
City
Menands
State
NY
Country
United States
Zip Code
12204