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Abstract:
The pleiotropic cytokine tumor necrosis factor a (TNFa) has previously been shown to regulate both the proliferation and differentiation of normal rat mammary epithelial cells (MEC) in primary culture (Ip et al, Endocrinology, 130, 2833-2844, 1992). Using agonistic antibodies (Genentech) specific to either the p55 or p75 TNF receptors, the individual roles of each TNF receptor in signalling these cellular responses was investigated. Under suboptimal (low EGF, 0.1 ng/ml) medium conditions in which TNFa can substitute for EGF for cell proliferation, the p55 receptor was found to be the sole mediator of TNFa-induced proliferation of MEC. Unexpectedly, antibodies directed against either TNF receptor had equivalent stimulatory effects on alveolar morphogenesis in suboptimal medium. Furthermore, the two receptors were found to have opposing effects on functional differentiation as assessed by casein accumulation. In both optimal (10 ng/ml EGF) and suboptimal media conditions, casein accumulation was inhibited in response to the p55 antibody, while it was stimulated by the antibody against the p75 receptor. Thus, these studies demonstrate that both TNF receptors are important for TNFa function in the mammary gland.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual rept. |
| Pages: |
36 |
| Report Date: |
26 JUL 95 |
| Contract Number: |
DAMD17-94-J-4158 |
| Report Number: |
A952003 |
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