The Role of Thrombin and its Receptors in Epithelial Malignancies: Lessons from a Transgenic Mouse Model and Transcriptional Regulation

摘要: The otherwise well-orchestrated epithelial sheets are disrupted when they acquire the ability to overexpress prototype mammalian thrombin receptor, human protease-activated receptor-1 (hPar1). This is exhibited by down-regulation of cell–cell contacts and alterations in cell–matrix interactions. notion that hPar1 one a series genes part malignant program stems from studies indicating expression directly correlates with tumor metastasis time-limited physiological invasion placenta uterus decidua. Our transgenic mouse model tissue-targeted overexpression mammary glands exhibits phenotype hyperplasia, characterized dense network ductal side branching accelerated proliferation. exhibit increased levels wnt-4 -7b, striking stabilization β-catenin. novel association between nuclear β-catenin may provide key determinant molecular pathway oncogenicity. While studying properties biology we demonstrated its role as survival factor protects cells undergoing apoptosis. Withdrawal gene leads selective apoptosis especially young sprouting blood vessels, whereas mature vessels remain unaffected. We also evidence showing tumors enhanced transcriptional activity. evaluated on basis elicited run-on transcription rate highly metastatic vs. low (on background equal stability rates). Indeed, have shown Egr-1 induced prostate cancer. In addition, suppressor p53 acts target genes, regulating level context given tumor. It still remains determine profile individual fingerprints specific motifs bind panel factors, well which critically involved altering according type