An investigation of microRNAs mapping to breast cancer related genomic gain and loss regions

Various regions of amplification or loss are observed in breast tumors as a manifestation of genomic instability. To date, numerous oncogenes or tumor suppressors on some of these regions have been characterized. An increasing body of evidence suggests that such regions also harbor microRNA genes with crucial regulatory roles in cellular processes and disease mechanisms, including cancer. Here, we investigated 35 microRNAs localized to common genomic gain and/or loss regions in breast cancers. To examine amplification or loss of these microRNAs as a result of genomic instability, we performed semiquantitative duplex polymerase chain reaction in 20 breast cancer cell lines, 2 immortalized mammary cell lines, and 2 normal DNA controls. A comprehensive DNA fold number change data for 35 microRNA genes on chromosomal gain/loss regions are presented in breast cancer cells. A 23% (8/35) of the investigated microRNAs showed significant fold number increases (greater than fourfold) compared to GAPDH in one or more of the breast cell lines. Although no homozygous deletions were detected, fold number decreases indicating potential loss regions were observed for 26% (9/35) of the investigated microRNAs. Such fold number changes may point out some of these microRNAs as potential targets of the genomic instability regions as oncogene and tumor suppressor candidates. © 2009 Elsevier Inc. All rights reserved

Comparing ‘apples with apples’: professional accounting practices in university classroom discourse

How are professional accounting practices represented in university classroom discourse and what are the implications of this for theory and practice in professional learning? Professional accounting practices order the world, and are also ordered. In reducing the complexities of social activity to abstract meanings that render it measurable, diverse and complex structures can be compared ‘apples with apples’. This study investigates the relocalization of professional accounting practices in university classroom discourse, working with tools from Legitimation Code Theory, systemic functional linguistics and critical discourse analysis. Findings draw on digital recordings of seminars presented by three lecturers in different subjects of a Master of Accounting program in an Australian metropolitan university. The analysis examines movements between context-independent and more context-dependent meanings in classroom discourse that mark shifts in emphasis from accounting as a system of representation, to accounting as interpersonal exchange. It considers two sets of social relations at play in the professional classroom: those between lecturers and students, and those within professional practice that are relocalized in classroom discourse. The framework developed in this study complements current research within the sociology of education. Discussion connects the analysis with recent explorations of knowledge practices in education within Legitimation Code Theory. It draws on foundational principles of a systemic functional model of language, considering the basis of professional practice and professional learning in interpersonal exchange. Conclusions are oriented towards theory and practice in professional learning, recognizing professional educators as agents of change and mediators of ways of thinking and acting in their field that are potentially transformative

EGF-SNX3-EGFR axis drives tumor progression and metastasis in triple-negative breast cancers

Epidermal growth factor receptor (EGFR) has critical roles in epithelial cell physiology. Over-expression and over-activation of EGFR have been implicated in diverse cancers, including triple-negative breast cancers (TNBCs), prompting anti-EGFR therapies. Therefore, developing potent therapies and addressing the inevitable drug resistance mechanisms necessitates deciphering of EGFR related networks. Here, we describe Sorting Nexin 3 (SNX3), a member of the recycling retromer complex, as a critical player in the epidermal growth factor (EGF) stimulated EGFR network in TNBCs. We show that SNX3 is an immediate and sustained target of EGF stimulation initially at the protein level and later at the transcriptional level, causing increased SNX3 abundance. Using a proximity labeling approach, we observed increased interaction of SNX3 and EGFR upon EGF stimulation. We also detected colocalization of SNX3 with early endosomes and endocytosed EGF. Moreover, we show that EGFR protein levels are sensitive to SNX3 loss. Transient RNAi models of SNX3 downregulation have a temporary reduction in EGFR levels. In contrast, long-term silencing forces cells to recover and overexpress EGFR mRNA and protein, resulting in increased proliferation, colony formation, migration, invasion in TNBC cells, and increased tumor growth and metastasis in syngeneic models. Consistent with these results, low SNX3 and high EGFR mRNA levels correlate with poor relapse-free survival in breast cancer patients. Overall, our results suggest that SNX3 is a critical player in the EGFR network in TNBCs with implications for other cancers dependent on EGFR activity.Chemical Immunolog