MUC1 alters oncogenic events and transcription in human breast cancer cells

INTRODUCTION: MUC1 is an oncoprotein whose overexpression correlates with aggressiveness of tumors and poor survival of cancer patients. Many of the oncogenic effects of MUC1 are believed to occur through interaction of its cytoplasmic tail with signaling molecules. As expected for a protein with oncogenic functions, MUC1 is linked to regulation of proliferation, apoptosis, invasion, and transcription. METHODS: To clarify the role of MUC1 in cancer, we transfected two breast cancer cell lines (MDA-MB-468 and BT-20) with small interfering (si)RNA directed against MUC1 and analyzed transcriptional responses and oncogenic events (proliferation, apoptosis and invasion). RESULTS: Transcription of several genes was altered after transfection of MUC1 siRNA, including decreased MAP2K1 (MEK1), JUN, PDGFA, CDC25A, VEGF and ITGAV (integrin α(v)), and increased TNF, RAF1, and MMP2. Additional changes were seen at the protein level, such as increased expression of c-Myc, heightened phosphorylation of AKT, and decreased activation of MEK1/2 and ERK1/2. These were correlated with cellular events, as MUC1 siRNA in the MDA-MB-468 line decreased proliferation and invasion, and increased stress-induced apoptosis. Intriguingly, BT-20 cells displayed similar levels of apoptosis regardless of siRNA, and actually increased proliferation after MUC1 siRNA. CONCLUSION: These results further the growing knowledge of the role of MUC1 in transcription, and suggest that the regulation of MUC1 in breast cancer may be more complex than previously appreciated. The differences between these two cell lines emphasize the importance of understanding the context of cell-specific signaling events when analyzing the oncogenic functions of MUC1, and caution against generalizing the results of individual cell lines without adequate confirmation in intact biological systems

On Partee’s “Noun Phrase Interpretation and Type-Shifting Principles”

Montague’s classic article “The Proper Treatment of Quantification in Ordinary English” (PTQ, 1973) treated all NP occurrences as quantificational. Partee’s article “Noun Phrase Interpretation and Type-Shifting Principles” (1987) reconciles PTQ’s uniform quantificational strategy with the older distinction between three NP types: entities, predicates and quantifiers. On top of this distinction, Partee introduces operators that allow shifting the denotation of an NP to a different type than the one it is initially assigned. Using these type-shifters, one and the same NP may receive each of the three interpretations. In addition to this synthesis of previous approaches, Partee’s article contains a rather elaborate analysis of predicative NPs, as well as insightful hints about the treatment of definite NPs, nominalization phenomena, plural, mass and generic NPs, and the mathematical principles underlying type-shifting. At a more global level, Partee’s article marks a methodological transition in formal semantics, highlighting general principles that are relevant to different languages and to different linguistic frameworks, rather than technicalities of artificial language fragments. This general account and the new ways it opened for semantic theory, together with the paper’s lucid and friendly style, have made “Noun Phrase Interpretation and Type-Shifting Principles” one of the modern classics in formal semantics. After some necessary background on NPs in PTQ, this review covers the main innovations in Partee’s article, and comments on the work and its influence

A mucoadhesive in situ gel delivery system for paclitaxel

MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyceryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at drug loads of 0.18%, 0.30%, and 0.54% (wt/wt), in Sorensen’s phosphate buffer (pH 7.4) at 37°C. Different mucin-producing cell lines (Calu-3>Caco-2) were selected for PTX transport studies. Transport of PTX from solution and gel delivery system was performed in side by side diffusion chambers from apical to basal (A-B) and basal to apical (B-A) directions. In vitro release studies revealed that within 4 hours, only 7.61%±0.19%, 12.0%±0.98%, 31.7%±0.40% of PTX were released from 0.18%, 0.30%, and 0.54% drugloaded gel formulation, respectively, in absence of Tween 80. However, in presence of surfactant (0.05% wt/vol) in the dissolution medium, percentages of PTX released were 28.1%±4.35%, 44.2%±6.35%, and 97.1%±1.22%, respectively. Paclitaxel has shown a polarized transport in all the cell monolayers with B-A transport 2 to 4 times higher than in the A-B direction. The highest mucin-producing cell line (Calu-3) has shown the lowest percentage of PTX transport from gels as compared with Caco-2 cells. Transport of PTX from mucoadhesive gels was shown to be influenced by the mucin-producing capability of cell