Human epidermal growth factor receptor isoform D (EGFR; isoform D) is a soluble protein from a 3 kb alternate mRNA transcript that arises from the human EGFR gene. Several studies have identified this circulating isoform of EGFR as a potential diagnostic biomarker for the detection of early stage of cancers. While the expression of the full-length EGFR (isoform A) is regulated by its cognate ligand, EGF, as well as by phorbol myristate acetate (PMA), no studies have examined the factors regulating the expression of EGFR isoform D. In this study, using breast cancer cell lines, we show that the HER receptor ligands, EGF and neuregulin (NRG-1β), as well as the phorbol ester, PMA, can increase the expression of EGFR isoform D, as well as isoform A. Our results, based on measurement of mRNA levels, suggest that EGF induced expression of both isoform A and isoform D occur through a mitogen activated protein kinase (MAPK)-dependent mechanism, and also suggest that protein kinase C is involved in PMA-induced regulation of both isoforms. We also demonstrate that NRG-1β increases isoform A and isoform D expression via the MAPK-dependent pathway, but this regulation occurs independently of phosphatidylinositol 3-kinase/Akt activation. These results suggest that regulation of EGFR isoform A and isoform D expression occur using similar mechanisms. Despite commonalities in the transcriptional regulation of these two EGFR isoforms, the half-lives of these two transcripts is quite different. Moreover, EGFR isoform D, unlike isoform A, is not post-transcriptionally modulated by EGFR activators in the breast cancer cell line MDA-MB-468.

Introduction: Researchers have begun to change their approach to training in the biomedical sciences through the development of communities of practice (CoPs). CoPs share knowledge across clinical and laboratory contexts to promote the progress of clinical and translational science. The Congressionally Directed Medical Research Programs' (CDMRP) Ovarian Cancer Academy (OCA) was designed as a virtual CoP to promote interactions among early career investigators (ECIs) and their mentors with the goal of eliminating ovarian cancer. Methods: A mixed-methods approach (surveys and interviews) was used to evaluate the effectiveness of the OCA for the eight ECIs and five mentors. Quantitative analysis included internal reliability of scales and descriptive statistics for each measure, as well as paired sample t-tests for Time 1 and Time 2. Qualitative data were analyzed for themes to discern which aspects of the program were useful and where more attention is needed. Results: Preliminary analyses reveal several trends, including the importance of training in grant writing to the ECI's productivity, as well as the value of peer mentorship. Conclusion: The results show that the OCA was an innovative and effective way to create a CoP with broad implications for the field of ovarian cancer research, as well as for the future of biomedical research training.