Doxycycline-inducible expression of SPARC/Osteonectin/BM40 in MDA-MB-231 human breast cancer cells results in growth inhibition

SPARC (secreted protein acidic and rich in cysteine)/BM40/Osteonectin is a matricellular protein with multiple effects on cell behaviour. In vitro, its major known functions are anti-adhesive and anti-proliferative, and it is associated with tissue remodelling and cancer in vivo. SPARC is overexpressed in many cancers, including breast cancer, and the effects of SPARC seem to be cell type-specific. To study the effects of SPARC on breast cancer, we transfected SPARC into the MDA-MB-231 BAG, human breast cancer cell line using the Tet-On inducible system. By western analysis, we found low background levels in the MDA-MB-231 BAG and clone X parental cells, and prominent induction of SPARC protein expression after doxycycline treatment in SPARC transfected clones X5, X21, X24 and X75. Induction of SPARC expression did not affect cell morphology or adhesiveness to collagens type I and IV, but it slowed the rate of proliferation in adherent cultures. Cell cycle analysis showed that SPARC slowed the progression to S phase. Doxycycline induction of SPARC also slowed the rate of monolayer wound closure in the cultured wound healing assay. Thymidine inhibition of proliferation abrogated this effect, confirming that it was due to anti-proliferation rather than inhibition of migration. Consistent with this, we were unable to detect any differences in migration and Matrigel outgrowth analysis of doxycycline-stimulated cells. We conclude that SPARC is inhibitory to human breast cancer cell proliferation, and does not stimulate migration, in contrast to its stimulatory effects reported for melanoma (proliferation and migration) and glioma (migration) cells. Similar growth repression by SPARC has been reported for ovarian cancer cells, and this may be a common feature among carcinomas.

The effect of gender context on children's social behaviour in a limited resources situation : an observational study

Knowing when to compete and when to cooperate to maximize opportunities for equal access to activities and materials in groups is critical to children's social and cognitive development. The present study examined the individual (gender, social competence) and contextual factors (gender context) that may determine why some children are more successful than others. One hundred and fifty-six children (M age=6.5 years) were divided into 39 groups of four and videotaped while engaged in a task that required them to cooperate in order to view cartoons. Children within all groups were unfamiliar to one another. Groups varied in gender composition (all girls, all boys, or mixed-sex) and social competence (high vs. low). Group composition by gender interaction effects were found. Girls were most successful at gaining viewing time in same-sex groups, and least successful in mixed-sex groups. Conversely, boys were least successful in same-sex groups and most successful in mixed-sex groups. Similar results were also found at the group level of analysis; however, the way in which the resources were distributed differed as a function of group type. Same-sex girl groups were inequitable but efficient whereas same-sex boy groups were more equitable than mixed groups but inefficient compared to same-sex girl groups. Social competence did not influence children's behavior. The findings from the present study highlight the effect of gender context on cooperation and competition and the relevance of adopting an unfamiliar peer paradigm when investigating children's social behavior.