Implications of increased tissue transglutaminase (TG2) expression in drug-resistant breast cancer (MCF-7) cells.

The development of resistance to chemotherapeutic drugs is a major obstacle to the successful treatment of breast cancer. Ways to block or overcome this resistance are objects of intense research. We have previously shown that cancer cells selected for resistance against chemotherapeutic drugs or isolated from metastatic tumor sites have high levels of a calcium-dependent protein crosslinking enzyme, tissue transglutaminase (TG2) but no direct link between TG2 and resistance was established. As TG2 can associate with the beta members of the integrin family of proteins, we hypothesized that TG2 promotes cell survival signaling pathways by activating integrins on the surface of these cells. To test this hypothesis, we studied the expression of TG2 and its interaction with various integrins in drug-resistant MCF-7 breast cancer cells. TG2 closely associated with beta1 and beta5 integrins on the surface of drug-resistant MCF-7 (MCF-7/Dox and MCF-7/RT) cells. The incubation of TG2-expressing drug-resistant MCF-7 cells on fibronectin (Fn)-coated surfaces strongly activated focal adhesion kinase, an event that leads to the activation of several downstream signaling pathways and, in turn, can confer apoptosis-resistant phenotype to cancer cells. The role of TG2 in Fn-mediated cell attachment, cell growth, and cell survival functions was further analysed by small interfering RNA (siRNA) approach. Inhibition of TG2 by siRNA-inhibited Fn-mediated cell attachment and cell survival functions in drug-resistant MCF-7 cells. We conclude that the expression of TG2 in breast cancer cells contributes to the development of the drug-resistance phenotype by promoting interaction between integrins and Fn.

Adult age differences in spatial memory: effects of distinctiveness and repeated experience.

Young (mean age = 25.0) and elderly (mean age = 65.0) women's memory for buildings in a large model town was assessed. Participants viewed and constructed the town on two trials. Building distinctiveness was manipulated by showing differentiated buildings with unique physical and functional properties (e.g., school, gas station), or nondifferentiated buildings that were not functionally distinct and only somewhat physically distinct (e.g., red cube-like structure with curved roof, yellow cube-like structure with flat roof). Building distinctiveness was further manipulated by verbally labeling or not labeling each building type. On Trial 1 young adults were more accurate than elderly adults only on the differentiated buildings; on Trial 2 this age difference was evident on differentiated and nondifferentiated buildings. Verbal labeling did not significantly affect construction accuracy. It was concluded that age differences occurred because elderly adults have more difficulty utilizing encoding strategies than young adults.

Young children's ability to infer spatial relationships: evidence from a large, familiar environment.

Young (mean age = 3-9) and old (mean age = 5-0) nursery school children were tested on their ability to infer spatial relationships in a large, familiar environment. Each child in the younger group was matched to a child of the same sex in the older group who had been attending the nursery school for the same number of months. Subjects were taken to 3 different locations in their nursery school and were asked to point to 5 targets on the school grounds. Older children were more accurate than younger children on nursery school targets, but children's spatial representations were relatively nonintegrated at both age levels. Consistent sex differences in favor of males were discussed in the context of a new framework that could potentially explain the appearance of sex differences on spatial tasks conducted in large-scale environments. It was concluded that very young children have difficulty inferring spatial relationships, even in a large, familiar environment. This difficulty seems to be due to a relative lack of symbolic capacity.

Distance distortions in children's cognitive maps: an examination of the information storage model.

Second graders (mean age = 7-8), fourth graders (mean age = 9-8), and sixth graders (mean age = 11-11) walked two paths located in and around their school. Children in the Unsegmented condition estimated the distance and time taken to walk a path that was relatively undifferentiated in terms of the number of qualitatively different areas of the school through which it passed. Children in the Segmented condition made the same estimates for a path that went through different areas (segments) of the school (i.e., cafeteria, hall, vestibule, and outside the building). Children at all three grade levels estimated that the distance traversed in the Segmented condition was longer than the distance in the Unsegmented condition. This difference was not significant on the time measure. It was concluded that (1) paths with a large number of segments are perceived as being longer than paths of the same length with fewer segments, (2) distances along paths with few segments are underestimated, (3) distances along paths with many segments may be overestimated as a function of developmental level, and (4) only younger children may have used time to estimate distance.

Children and adults' distance estimations in a large-scale environment: effects of time and clutter.

In two experiments adults (mean age = 19-5), sixth graders (mean age = 11-8), fourth graders (mean age = 9-8), and second graders (mean age = 7-8) walked a straight line distance through a large-scale environment. Subjects were then asked to estimate the time taken to traverse each half of the walk and to estimate the distance between objects seen along the walk. In Experiment 1 each half of the walk was traversed in the same amount of time but contained a different number of objects (clutter). Time and distance estimates were related, but were not affected by the number of intervening objects encountered between locations. In Experiment 2 subjects again encountered a different number of objects along each half of the walk but each half was traversed in varying amounts of time. Again, time and distance estimates were related, and there was no clutter effect. There were no consistent developmental differences across the two experiments. It was concluded that (1) Thorndyke's clutter effect does not occur across all types of spatial cognition tasks, and (2) children and adults tend to relate time and distance across a variety of distance estimation tasks.

Adults' mental rotation of spatial information: effects of age, sex and cerebral laterality.

The mental rotation ability of young (mean age = 25.3) and elderly adults (mean age = 65.3) was assessed. Preferred cerebral hemisphere for information processing was determined by asking subjects questions designed to elicit lateral eye movements. Subjects were classified as preferring the right hemisphere, the left hemisphere, or neither hemisphere (mixed dominance). Participants were then given a task requiring them to match rotated blocks used in the Shepard and Metzler [13] experiment. Young subjects were more accurate than elderly subjects and males were more accurate than females at both age levels. There was no difference in accuracy as a function of preferred hemisphere for information processing. It was concluded that: (1) there may be no relationship between preferred hemisphere for processing and accuracy on a mental rotation task (2) there are age-related changes in the accuracy of mental rotation, and (3) males perform more accurately than females throughout adulthood on mental rotation tasks.

Spatial knowledge of young and elderly adults: scene recognition from familiar and novel perspectives.

Thirty young adults (mean age = 25.3) and 30 elderly adults (mean age = 65.3) were tested on a memory task in which they were asked to recognize environmental scenes from familiar and novel perspectives. Participants initially viewed slides of 10 business and 10 residential street intersections. Pairs of intersections were then presented and subjects were asked to select the intersection viewed previously. During the recognition phase subjects saw the intersections from the original perspective (0 degrees), rotated 90 degrees from the original perspective, or rotated 180 degrees from the original perspective. Young adults were more accurate than elderly adults and accuracy was greater for business than residential scenes at both age levels. Subjects were more accurate in the 0 than 180 degree condition, while performance in the 90 degree condition was significantly less accurate than in the other two conditions. These results indicate that (1) young adults have better recognition memory than elderly adults for real world scenes, and (2) environmental differentiation aids recognition memory for spatial locations.

Effects of motor activity on children's intentional and incidental memory for spatial locations.

Kindergartners (means = 57) and third graders (means = 8-7) encountered a large model town in 1 of 3 conditions of motor involvement with the environment: standing, riding, or walking. Half the children in each motor condition were instructed to remember the location of the buildings (international memory), while the remaining children were not given specific memory instructions (incidental memory). Only the kindergartners' accuracy increased as a function of the amount of motor activity. There was no difference between intentional and incidental memory conditions. It was concluded that: (1) Kindergartners depend on motor activity more than third graders to learn about the location of objects in an unfamiliar environment; and (2) the complexity of the spatial task was primarily responsible for equivalent performance in the intentional and incidental memory conditions.

Lateral eye movements and the recall of spatial information in a familiar, large-scale environment.

The relationship between cerebral asymmetry and memory for locations in a familial large-scale environment was examined. Subjects were classified as showing a preference for right or left hemisphere processing on the basis of the direction of their lateral eye movements. Knowledge of the locations of 10 landmarks in a familial large-scale space was assessed. No differences were found between right and left movers. It was concluded that memory for the location of landmarks in a familiar large-scale space is processed equally effectively by those who prefer to process information with the right or left hemisphere.

Spatial knowledge of ambulatory and wheelchair-confined nursing home residents.

The spatial knowledge of ambulatory (Mean Age=80.5) and wheelchair-confined (Mean Age=76.2) nursing home residents was assessed. Subjects were asked to locate the position of salient nursing home landmarks on a schematic of the nursing home. The results suggested no difference in the spatial knowledge of ambulatory and wheelchair-confined residents. Age and frequency of encountering landmarks were related to accuracy while time of residency was unrelated to accuracy.

Age differences in acoustic and semantic recognition memory.

Patterns of information encoding were examined across a wide age range of subjects. Subjects aged 8-, 10-, 24-, 66-, and 75-yr. were administered a recognition memory task involving both acoustically and semantically related distractor words. The errors and latencies indicated no age-difference in encoding patterns. A comparison of errors for 8-, 10-, and 24-yr.-olds alone, however, indicated a shift from acoustic tp se,amtoc encoding style between the ages of 8 and 10.

Developmental issues in cognitive mapping: the selection and utilization of environmental landmarks.

2 studies were conducted to investigate developmental differences in the ability to select and use environmental landmarks for cognitively organizing distance information from a walk. In experiment 1, second-grade, fifth-grade, and college subjects viewed a simulated walk and selected scenes that were high in potential landmark value. In experiment 2, children from the same grade levels first viewed the walk and then ranked distances among either the test scenes most frequently selected by their peers or those selected most frequently by adults. Results indicated that (a) adults and children may not spontaneously select the same features as real-world landmarks; (b) children are less capable than adults in judging the value of potential landmarks as distance cues; and (c) the ability to use environmental landmarks as cues for distance information developmentally precedes the ability to assess this potential information value.

The development of cognitive maps of large- and small-scale spaces.

Kindergartners, second, and fifth graders made repeated trips through a large- or small-scale model town, and then constructed from memory the layout of buildings in either a large- or small-scale space. Accuracy of construction increased as a function of developmental level and repeated trips through the town. Children's constructions were most accurate when they were tested in the same-scale environment as that in which they developed their spatial knowledge; accuracy was impaired significantly only when children were exposed to a small space and then reconstructed in a large space. Results were interpreted in terms of a "competence-load trade-off."