cyclic-gmp and Paraneoplastic-Syndromes

The envelope protein (gp52) of the mouse mammary tumor virus (MMTV) can stimulate RNA synthesis via binding to its cellular receptor on mammary epithelium. This effect was mimicked by either nitric oxide (NO) or 8-bromo-cGMP and was blocked by an NO inhibitor. Furthermore, the effects of gp52 and 8-bromo-cGMP were not additive at maximal concentrations, suggesting that they were using the same signaling route. Finally, gp52 elevated cGMP levels in mammary epithelium. These data suggest that gp52 activates the following transduction pathway in this tissue: gp52-->NO synthase-->NO-->soluble guanylate cyclase cGMP RNA synthesis. In contrast to the mammary gland, gp52 inhibited RNA synthesis in the diaphragm. However, the effect was again mimicked by NO, blocked by an NO inhibitor, and the effects of gp52 and NO were not additive. Therefore, it appears that gp52 is using the NO-cGMP pathway in both tissues, but that muscle tissue may be more susceptible to the toxic effects of NO.

Topics: Animals; Antigens, Viral, Tumor; Cyclic GMP; Diaphragm; Female; Glycoproteins; In Vitro Techniques; Mammary Glands, Animal; Mammary Tumor Virus, Mouse; Mice; Mice, Inbred C3H; Nitric Oxide; Nitric Oxide Synthase; Paraneoplastic Syndromes; Retroviridae Infections; Second Messenger Systems; Signal Transduction; Tumor Virus Infections; Viral Envelope Proteins