The Role and Regulation of TNF-Alpha in Normal Rat Mammary Gland During Development and in Breast Cancer.
Annual rept. 1 Jul 95-30 Jun 96,
HEALTH RESEARCH INC BUFFALO NY
Pagination or Media Count:
To determine if TNFalpha plays a physiological role in normal mammary gland development, TNF and TNF receptor expression were measured in epithelial cells MEC isolated from mammary glands of virgin, pregnant, lactating, and post-lactational day 7 of involution rats. TNF mRNA increased significantly during pregnancy, then decreased during lactation and involution. The 26-kDa, transmembrane form of TNF protein, undetectable in MEC from virgin rats, increased throughout pregnancy and lactation and disappeared during involution. In contrast, p55 TNF receptor TNFR mRNA levels peaked in early lactation and declined thereafter, while p75 TNFR mRNA levels rose steadily through lactation. Using specific agonistic antibodies, the p55 TNFR was found to be the sole mediator of TNF-induced proliferation. Intriguingly, the two receptors had opposing effects on functional differentiation casein accumulation, with inhibition occurring through the p55 receptor and stimulation through p75. Lastly, in DMBA- and NMU-induced mammary tumors, both TNF and TNFR mRNA levels were found to be decreased in comparison to normal MEC. Taken together, these result suggest that TNF plays a role in the growth and development of the mammary gland, and may mediate different effects.
- Medicine and Medical Research