Stress, associated with the incidence, prognosis and relapse of breast cancer, also influences the immune/hematopoietic-neural axis partly through the release of neurohormones. Since cancer is partly due to a failure of the immune surveillance, we hypothesize that the neuroendocrine system is the link between stress and breast cancer development. In this study, we examined the role of neurokinins, PPT-I, and their receptors, NK-1 and NK-2, as neuroendocrine parameters. The rationale being their: 1) sensitivity to stress, 2) angiogenic properties, 3) proliferative effects, 4) expression in primary tumors, 5) sensitivity to stress-associated neurohormones and hypoxia. By quantitative RT-PCR, ELISA and in situ hybridization, we have found that PPT-I, NK-1 and NK-2 are constitutively expressed in 7 different breast cancer cell lines while background levels were detected in normal mammary epithelial. Specific NK-1 and NK-2 antagonists inhibited breast cancer cell proliferation suggesting an autocrine role for PPT-I peptides. Using an in vitro translation assay, we have shown that cytosolic extracts from breast carcinomas increase β-PPT-I translation. Current studies are designed to analyze the putative translational factor with particular sequences derived from PPT-I mRNA folding. The 'uniqueness' of these factors are also being addressed. These studies are novel attempts to map molecular pathways that connect stress and breast cancer development and provide strategies for therapeutic interventions. The data suggest that PPT-I gene expression may be a downstream event in neuroendocrine-mediated mechanisms of breast cancer development.
|Original language||English (US)|
|State||Published - Mar 20 1998|
All Science Journal Classification (ASJC) codes
- Molecular Biology