Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.     

A DNA-binding element for a steroid receptor-binding factor is flanked by dual nuclear matrix DNA attachment sites in the c-myc gene promoter

The receptor-binding factor (RBF) for the avian oviduct progesterone (Pg) receptor (PR) has previously been shown to be a unique 10-kDa nuclear matrix protein that generates high affinity PR-binding sites on avian DNA. This paper describes the use of Southwestern blot and DNA gel shift analyses with RBF protein to identify a minimal 54-base pair RBF-binding element in the matrix-associated region (MAR) of the Pg-regulated c-myc gene promoter. This element contains a 5'-GC-rich domain and a 3'-AT-rich domain, the latter of which has a homopurine/homopyrimidine structure. The gel shift assays required the generation of an RBF-maltose fusion protein (RBF-MBP), which specifically binds this element and is supershifted when the anti-RBF polyclonal antibody is added. Computer analysis of the full-length amino acid sequence for RBF predicts a DNA-binding motif involving a beta-sheet structure at the N-terminal domain. Southern blot analyses using nuclear matrix DNA suggests that there are dual MAR sites in the c-myc promoter, which flank an intervening domain containing the RBF element. The co-transfection of this MAR sequence, containing the RBF element and cloned into a luciferase reporter vector, together with an RBF expression vector construct, into steroid treated human MCF-7 cells, results in a decrease of the c-myc promoter activity relative to control transfections containing only the parent vector of the RBF expression construct. These data suggest that a unique chromatin/nuclear matrix structure, composed of the RBF-DNA element complex which is flanked by nuclear matrix attachment sites, serves to bind the PR and repress the c-myc promoter.     

Evidence for two types of spatial representations: Hemispheric specialization for categorical and coordinate relations.

Analyses of human object recognition abilities led to the hypothesis that 2 kinds of spatial relation representations are used in human vision. Evidence for the distinction between abstract categorical spatial relation representations and specific coordinate spatial relation representations was provided in 4 experiments. These results indicate that Ss make categorical judgments—on/off, left/right, and above/below—faster when stimuli are initially presented to the left cerebral hemisphere, whereas they make evaluations of distance—in relation to 2 mm, 3 mm, or 1 in. (2.54 cm)—faster when stimuli are initially presented to the right cerebral hemisphere. In addition, there was evidence that categorical representations developed with practice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Learning about tools in infancy.

These experiments explored the role of prior experience in 12- to 18-month-old infants' tool-directed actions. In Experiment 1, infants' use of a familiar tool (spoon) to accomplish a novel task (turning on lights inside a box) was examined. Infants tended to grasp the spoon by its handle even when doing so made solving the task impossible (the bowl did not fit through the hole in the box, but the handle did) and even though the experimenter demonstrated a bowl-grasp. In contrast, infants used a novel tool flexibly and grasped both sides equally often. In Experiment 2, infants received training using the novel tool for a particular function; 3 groups of infants were trained to use the tool differently. Later, infants' performance was facilitated on tasks that required infants to grasp the part of the tool they were trained to grasp. The results suggest that (a) infants' prior experiences with tools are important to understanding subsequent tool use, and (b) rather than learning about tool function (e.g., hammering), infants learn about which part of the tool is meant to be held, at least early in their exposure to a novel tool. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Desire and the couch: Perspectives from both sides of the analytic encounter.

This report summarizes the panel held at the 109th Annual Convention, American Psychological Association, August 26, 2001, San Francisco. The chair was William Glover and the speakers were Samuel Gerson, Karen Maroda, and Andre Patsalides. The invited symposium was directed at discussing different perspectives related to the presence of desire in the analytic process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)