Pharmacological Inhibition of CDK8 in Triple-Negative Breast Cancer Cell Line MDA-MB-468 Increases E2F1 Protein, Induces Phosphorylation of STAT3 and Apoptosis.

Cyclin-dependent kinase 8 (CDK8) has been identified as a colon cancer oncogene. Since this initial observation, CDK8 has been implicated as a potential driver of other cancers including acute myelogenous leukemia (AML) and some breast cancers. Here, we observed different biological responses to CDK8 inhibition among colon cancer cell lines and the triple-negative breast cancer (TNBC) cell line MDA-MB-468. When treated with CDK8 inhibitor 4, all treated cell lines responded with decreased cell viability and increased apoptosis. In the MDA-MB-468 cell line, the decrease in cell viability was dependent on increased phosphorylation of signal transducer and activator of transcription 3 (STAT3), which is not observed in the colon cancer cell lines. Furthermore, increased STAT3 phosphorylation in 4 treated MDA-MB-468 cells was dependent on increased transcription factor E2F1 protein. These results are consistent with previous reports of exogenous expression of E2F1-induced apoptosis in MDA-MB-468 cells.

The Effects of Practice-Based Training on Graduate Teaching Assistants' Classroom Practices.

Evidence-based teaching is a highly complex skill, requiring repeated cycles of deliberate practice and feedback to master. Despite existing well-characterized frameworks for practice-based training in K-12 teacher education, the major principles of these frameworks have not yet been transferred to instructor development in higher educational contexts, including training of graduate teaching assistants (GTAs). We sought to determine whether a practice-based training program could help GTAs learn and use evidence-based teaching methods in their classrooms. We implemented a weekly training program for introductory biology GTAs that included structured drills of techniques selected to enhance student practice, logic development, and accountability and reduce apprehension. These elements were selected based on their previous characterization as dimensions of active learning. GTAs received regular performance feedback based on classroom observations. To quantify use of target techniques and levels of student participation, we collected and coded 160 h of video footage. We investigated the relationship between frequency of GTA implementation of target techniques and student exam scores; however, we observed no significant relationship. Although GTAs adopted and used many of the target techniques with high frequency, techniques that enforced student participation were not stably adopted, and their use was unresponsive to formal feedback. We also found that techniques discussed in training, but not practiced, were not used at quantifiable frequencies, further supporting the importance of practice-based training for influencing instructional practices.