HER-2 overexpression differentially alters transforming growth factor-β responses in luminal versus mesenchymal human breast cancer cells

INTRODUCTION: Amplification of the HER-2 receptor tyrosine kinase has been implicated in the pathogenesis and aggressive behavior of approximately 25% of invasive human breast cancers. Clinical and experimental evidence suggest that aberrant HER-2 signaling contributes to tumor initiation and disease progression. Transforming growth factor beta (TGF-β) is the dominant factor opposing growth stimulatory factors and early oncogene activation in many tissues, including the mammary gland. Thus, to better understand the mechanisms by which HER-2 overexpression promotes the early stages of breast cancer, we directly assayed the cellular and molecular effects of TGF-β1 on breast cancer cells in the presence or absence of overexpressed HER-2. METHODS: Cell proliferation assays were used to determine the effect of TGF-β on the growth of breast cancer cells with normal or high level expression of HER-2. Affymetrix microarrays combined with Northern and western blot analysis were used to monitor the transcriptional responses to exogenous TGF-β1 in luminal and mesenchymal-like breast cancer cells. The activity of the core TGF-β signaling pathway was assessed using TGF-β1 binding assays, phospho-specific Smad antibodies, immunofluorescent staining of Smad and Smad DNA binding assays. RESULTS: We demonstrate that cells engineered to over-express HER-2 are resistant to the anti-proliferative effect of TGF-β1. HER-2 overexpression profoundly diminishes the transcriptional responses induced by TGF-β in the luminal MCF-7 breast cancer cell line and prevents target gene induction by a novel mechanism that does not involve the abrogation of Smad nuclear accumulation, DNA binding or changes in c-myc repression. Conversely, HER-2 overexpression in the context of the mesenchymal MDA-MB-231 breast cell line potentiated the TGF-β induced pro-invasive and pro-metastatic gene signature. CONCLUSION: HER-2 overexpression promotes the growth and malignancy of mammary epithelial cells, in part, by conferring resistance to the growth inhibitory effects of TGF-β. In contrast, HER-2 and TGF-β signaling pathways can cooperate to promote especially aggressive disease behavior in the context of a highly invasive breast tumor model

Human-Oriented Approach in Forming of Key Competences of Civil Servants in the Conditions of Digital Transformation of the Economy

The article is devoted to the issues of applying a human-focused approach in determining the competencies of civil servants and the directions of their qualifications development. The aim of the study is to develop a model of key competencies of state civil servants taking into account the requirements of official regulations, qualification requirements for professional knowledge and skills of civil servants, as reflected in regulatory and legal documents, as well as trends in a competence-based focus approach to development of potential of employees. There have been given the results of an expert survey conducted in 2018 among organizations of the public civil service of three constituent entities of the Russian Federation. The analysis showed that despite the transition of the civil service to the digital technologies and services, there had been paid not much attention to change the behavioral attitudes of personnel and their readiness for innovations. So, skills in using methods of project management, development of creative capabilities, empathy, and mentoring are not highly appreciated. As a rule, during choosing areas of advanced training, they prefer professional skills training programs, ignoring other formats aimed at development of the important soft skills in the digital economy. The use of a competence-based approach to the formation of a competencies model, methods of the analysis and in the synthesis of quantitative and qualitative parameters of the existing career management system of public civil servants allowed to substantiate the basic principles of introducing a human-oriented approach to the personnel work of state bodies. The authors proposed a model of key competencies for various groups of civil service positions. The main conclusions are formulated on the need to use analytical tools to monitor the current level of public civil service competencies development, as well as to develop recommendations about modeling in further professional and career growth. There has been proposed a classification of the “soft” skills and development instruments needed for the improvement of the professional activity of civil servants in a digitalization of the economy. The importance of the human-oriented approach in the competency model is caused by need of the work transformation of the public civil service under the conditions of the digital economy

Automating Processes of Personnel Motivation Management in the Context of Implementing a Principle of Social Justice

The paper is devoted to studying the experience of Russian organizations in solving the problem of automation of one of the main HR functions — motivation and work incentives of employees of the organizations. After personnel administration, HR motivation management has become the second HR function, which is successfully automated in Russian organizations. The methodological basis of the study is a modern understanding of the theory of human capital. The research methodology provides for the reconstruction of the labor stimulation process based on the development and implementation of key performance indicators in conjunction with the automation processes of operational HR processes. The work results as follows: systematization of software that automates the basic processes for staff motivation; development of recommendations for HR departments on the development and implementation of an automated system of main performance indicators. The authors have proved that the correctly implemented automation of the HR function to calculate compensation and benefits during the transition to a more complex remuneration system makes it possible in practice not just to increase the economic results of the organization, but also to implement the fundamental principle of effective management — the principle of a fair assessment of the results of each employee’s work

Effective university contract management system in the context of professional standards implementation

Статья описывает опыт Финансового университета по адаптации системы эффективного контракта в условиях перехода на профессиональный стандарт «Педагог профессионального обучения, профессионального образования и дополнительного профессионального образования». Представленная в статье информация включает в себя практический кейс с решением и отражает задачу по внедрению критериев и показателей эффективности научно-педагогических работников (НПР) с учетом пересмотра их трудовых функций под влиянием профессионального стандарта. Кейс. Влияние профессионального стандарта на систему управления эффективным контрактом и эффективность вуза. Исходные показатели: Профессиональный стандарт. Стратегия развития Финансового университета. Показатели эффективности из Методики балльно-рейтинговой системы по оценке персонального вклада научно-педагогических работников. Трудовые договора с научно-педагогическими работниками. Должностные инструкции научно-педагогических работников. Индивидуальные планы работ научно-педагогических работников. Задача, отраженная в статье, решена в результате вовлечения ключевых специалистов в проектные и рабочие группы, деятельность которых связана с поэтапной реализацией системы эффективного контракта в Финансовом университете. Результат выполненных работ: усовершенствованные и переработанные формы трудовых договоров с научно-педагогическими работниками; нормы их времени; локальные нормативные акты, регулирующие оплату труда; система индивидуального планирования; разработанные и внедренные формы оценочных листов, библиотека критериев и показателей эффективности; создание комиссии по оценке эффективности деятельности научно-педагогических работников. Практическими рекомендациями, сформулированными в статье, стало описание процесса интеграции существующей системы по регулированию деятельности научно-педагогических работников и их оплаты труда под новые условия, связанные с переходом на эффективный контракт с учетом трудовых функций и трудовых действий, конкретизированных профессиональным стандартом. В качестве научной новизны статьи стоит выделить практический опыт пересмотра трудовых функций научно-педагогических работников, критериев и показателей эффективности их деятельности под влиянием профессионального стандарта педагога и стратегии развития Финансового университета. Ценностью данной статьи являются рекомендации для руководителей высшего звена государственных вузов по выстраиванию целостного подхода к управлению системой эффективного контракта.The article describes experience of University of Finance in adapting effective contract system in the context of transition to professional standard “Lecturer in the field of professional training, education and supplementary professional education”. Information presented in the article includes a case with solution and reflects the task of introducing efficacy criteria and indicators of academic and teaching staff (ATS) considering review of their labor functions according to professional standard. Case. Influence of professional standard on the system of effective contract management and university efficacy. Initial indicators: Professional standard. Development strategy of the University of Finance. 3. Efficacy indicators from score and rating system on evaluating personal input of academic and teaching staff members. Labor agreements with academic and teaching staff members. 5. Duties of academic and teaching staff members. Individual workplan for academic and teaching staff members. The task reflected in the article is solved as a result of involving key specialists into project and workgroups activities of which are related to stage by stage implementation of effective contract system at the University of Finance. The results of performed activities: - Improved and reformulated forms of labor contracts with academic and teaching staff members; their time norms; local norms regulating salary; individual planning system; - Designed and implemented evaluation sheets, library of efficacy criteria and indicators; - Creation of commission on evaluating efficacy of academic and teaching staff activities. Practical recommendations formulated in the article take a form of description of a process of integrating existing system of regulating academic and teaching staff activities and their salary into new context related to using effective contract considering labor functions and activities, described in detail by professional standard. Academic novelty is in practical experience of reviewing academic and teaching staff labor functions, criteria and indicators of their efficacy according to professional standard of teacher and University of Finance development strategy. The value of this article is in recommendations for university top managers concerning creating overall approach to managing effective labor contract system