The Effect of Tau and Taxol on Polymerization of MCF7 Microtubules In Vitro.

Overexpression of Tau protein in breast cancer cells is identified as an indicator for potential resistance to taxane-based therapy. As reported findings have been obtained mostly from clinical studies, the undetermined underlying mechanism of such drug resistance needs to be thoroughly explored through comprehensive in vitro evaluations. Tau and Taxol bind to the beta tubulin site in microtubules' structure.

A Confirmation for the Positive Electric Charge of Bio-Molecular Motors through Utilizing a Novel Nano-Technology Approach In Vitro.

Molecular motors are microtubule-based proteins which contribute to many cell functions, such as intracellular transportation and cell division. The details of the nature of the mutual interactions between motors and microtubules still needs to be extensively explored. However, electrostatic interaction is known as one of the key factors making motor-microtubule association possible.

The regulatory effect of Tau protein on polymerization of MCF7 microtubules .

Growing evidence continues to point toward the critical role of beta tubulin isotypes in regulating some intracellular functions. Changes that were observed in the microtubules' intrinsic dynamics, the way they interact with some chemotherapeutic agents, or differences on translocation specifications of some molecular motors along microtubules, were associated to their structural uniqueness in terms of beta tubulin isotype distributions. These findings suggest that the effects of microtubule associated proteins (MAPs) may also vary on structurally different microtubules.

Electrostatic differences: A possible source for the functional differences between MCF7 and brain microtubules.

Recent studies suggested a link between diversity of beta tubulin isotypes in microtubule structures and the regulatory roles that they play not only on microtubules' intrinsic dynamic, but also on the translocation characteristics of some of the molecular motors along microtubules. Remarkably, unlike porcine brain microtubules, MCF7 microtubules are structured from a different beta tubulin distribution. These types of cancer microtubules show a relatively stable and slow dynamic.

Modeling multi-mutation and drug resistance: analysis of some case studies.

Background: Drug-induced resistance is one the major obstacles that may lead to therapeutic failure during cancer treatment. Different genetic alterations occur when tumor cells divide. Among new generations of tumor cells, some may express intrinsic resistance to a specific chemotherapeutic agent.

MCF7 microtubules: Cancer microtubules with relatively slow and stable dynamic in vitro.

There is known to be significant diversity of β-tubulin isoforms in cells. However, whether the functions of microtubules that are polymerized from different distributions of beta isotypes become distinct from one another are still being explored. Of particular interest, recent studies have identified the role that different beta tubulin isotypes carry in regulating the functions of some of the molecular motors along MCF7, or breast cancer, microtubules.

Distinctions between dynamic characteristics of the single EG5 motor protein along neural vs. cancerous microtubules.

The kinesin 5 motor contributes critically to mitosis, and is often upregulated in cancer. In vitro motility studies of kinesin 5 moving along bovine brain microtubules indicate that the motors have limited processivity. Cancer cells have abnormal mitotic behavior, so one might wonder whether the functional properties of kinesin 5 change in such a background.

The Contribution of the C-Terminal Tails of Microtubules in Altering the Force Production Specifications of Multiple Kinesin-1.

The extent to which beta tubulin isotypes contribute to the function of microtubules and the microtubule-driven transport of molecular motors is poorly understood. The major differences in these isotypes are associated with the structure of their C-terminal tails. Recent studies have revealed a few aspects of the C-terminal tails' regulatory role on the activities of some of the motor proteins on a single-molecule level.

Microtubule C-Terminal Tails Can Change Characteristics of Motor Force Production.

Control of intracellular transport is poorly understood, and functional ramifications of tubulin isoform differences between cell types are mostly unexplored. Motors' force production and detachment kinetics are critical for their group function, but how microtubule (MT) details affect these properties--if at all--is unknown. We investigated these questions using both a vesicular transport human kinesin, kinesin-1, and also a mitotic kinesin likely optimized for group function, kinesin-5, moving along either bovine brain or MCF7(breast cancer) MTs.

Modeling drug resistance in a conjoint normal-tumor setting.

Background: In this paper, we modify our previously developed conjoint tumor-normal cell model in order to make a distinction between tumor cells that are responsive to chemotherapy and those that may show resistance.

Results: Using this newly developed core model, the evolution of three cell types: normal, tumor, and drug-resistant tumor cells, is studied through a series of numerical simulations. In addition, we illustrate critical factors that cause different dynamical patterns for normal and tumor cells.

Kinesin-1 translocation: Surprising differences between bovine brain and MCF7-derived microtubules.

While there have been many single-molecule studies of kinesin-1, most have been done along microtubules purified from bovine or porcine brain, and relatively little is known about how variations in tubulin might alter motor function. Of particular interest is transport along microtubules polymerized from tubulin purified from MCF7 breast cancer cells, both because these cells are a heavily studied model system to help understand breast cancer, and also because the microtubules are already established to have interesting polymerization/stability differences from bovine tubulin, suggesting that perhaps transport along them is also different. Thus, we carried out paired experiments to allow direct comparison of in vitro kinesin-1 translocation along microtubules polymerized from either human breast cancer cells (MCF7) or microtubules from bovine brain.

Measuring the persistence length of MCF7 cell microtubules in vitro.

The dynamic and mechanical properties of mammalian neural microtubules have been widely studied; however, similar knowledge about these properties is limited for non-neural microtubules, which, unlike neural microtubules, consist of different β-tubulin isotypes. In this study, we report, for the first time, an estimated value for the persistence length of a single non-neural microtubule polymerized from purified tubulin from human breast cancer cell lines (MCF7 tubulin). The method of measurement is based on an analysis of the local curvature of a microtubule as a result of thermal fluctuations.

Modeling the effects of a simple immune system and immunodeficiency on the dynamics of conjointly growing tumor and normal cells.

In this paper, we develop a theoretical contribution towards the understanding of the complex behavior of conjoint tumor-normal cell growth under the influence of immuno-chemotherapeutic agents under simple immune system response. In particular, we consider a core model for the interaction of tumor cells with the surrounding normal cells. We then add the effects of a simple immune system, and both immune-suppression factors and immuno-chemotherapeutic agents as well.