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| The role of apoptosis in creating and maintaining luminal space with normal and oncogene-expressing mammary acini |
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| Author(s): Debnath J, Mills KR, Collins NL, Reginato MJ, Muthuswamy SK, Brugge JS |
| Source: CELL Volume: 111 Issue: 1 Pages: 29-40 Published: OCT 4 2002 |
| Times Cited: 215 References: 49 |
| Abstract: We have utilized in vitro three-dimensional epithelial cell cultures to analyze the role of apoptosis in the formation and maintenance of a hollow glandular architecture. Lumen formation is associated with the selective apoptosis of centrally located cells; this apoptosis follows apicobasal polarization and precedes proliferative suppression during acinar development. Notably, either inhibiting apoptosis (by exogenously expressing antiapoptotic Bcl family proteins) or enhancing proliferation (via Cyclin D1 or HPV E7 overexpression) does not result in luminal filling, suggesting glandular architecture is resistant to such isolated oncogenic insults. However, the lumen is filled when oncogenes that enhance proliferation are coexpressed with those that inhibit apoptosis, or when ErbB2, which induces both activities, is activated by homodimerization. Hence, apoptosis can counteract increased proliferation to maintain luminal space, suggesting that tumor cells must restrain apoptosis to populate the lumen. |
| Document Type: Article |
| Language: English |
| Reprint Address: Brugge, JS (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA |
Addresses:
1. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
2. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 601RQ |
| ISSN: 0092-8674 |
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