Significance of mast cell distribution in placental tissue and membranes in spontaneous preterm birth.

BACKGROUND: Preterm birth is a common cause of adverse neonatal and childhood outcomes, in both the short and long term. Preterm labor is commonly associated with inflammation at the maternal-fetal interface. There is some indirect evidence that mast cells (MCs) might represent a link between hormonal influences and local reactions leading to the onset of labor. PATIENTS AND METHODS: The placentas and membranes of 51 uncomplicated spontaneous term births were compared to those from 50 spontaneous preterm births. Immunohistochemical staining for MC tryptase was undertaken allowing MC concentration, location, and degranulation status to be determined. Regression modeling was used to compare results. RESULTS: There were no significant differences in the demographic characteristics of the two cohorts. There were significantly more MCs in the decidua for term births than preterm births (P=0.03). The presence of histological chorioamnionitis did not affect MC concentrations. CONCLUSION: Despite evidence suggesting a possible role for MCs in spontaneous preterm birth, this study found that the concentration of decidual MCs was in fact significantly lower in preterm compared to term birth.

Chromatinized protein kinase C-θ directly regulates inducible genes in epithelial to mesenchymal transition and breast cancer stem cells.

Epithelial to mesenchymal transition (EMT) is activated during cancer invasion and metastasis, enriches for cancer stem cells (CSCs), and contributes to therapeutic resistance and disease recurrence. Signal transduction kinases play a pivotal role as chromatin-anchored proteins in eukaryotes. Here we report for the first time that protein kinase C-theta (PKC-θ) promotes EMT by acting as a critical chromatin-anchored switch for inducible genes via transforming growth factor ß (TGF-ß) and the key inflammatory regulatory protein NF-κB. Chromatinized PKC-θ exists as an active transcription complex and is required to establish a permissive chromatin state at signature EMT genes. Genome-wide analysis identifies a unique cohort of inducible PKC-θ-sensitive genes that are directly tethered to PKC-θ in the mesenchymal state. Collectively, we show that cross talk between signaling kinases and chromatin is critical for eliciting inducible transcriptional programs that drive mesenchymal differentiation and CSC formation, providing novel mechanisms to target using epigenetic therapy in breast cancer.