Creating cellular model for studying novel mechanisms of transcriptional reprogramming in breast carcinogenesis

الموضوعات

علوم تطبيقية وتكنولوجية

الملخص

Breast cancer is one of the most common and heterogonous cancer types, and the first cause of death related to cancer in women worldwide. Breast cancer is triggered by endogenous and/or exogenous factors. These factors lead to critical mutations and/or eipmutations in important genes including oncogenes and tumor suppresser genes. These genetic and epigenetic changes lead to cancer initiation and cancer progression. During these processes, cells gain alteration and dysregulation in gene expression at different levels. The most important and critical level of gene expression alteration in cancer is the transcriptional level. Our current project is part of a larger project, in which we hypothesized that breast cancer transformation might have common transcriptional reprograming events, that are associated with misregulation in gene expression, which reflects on cellular activity and homeostasis. In this part of the project, the aim was to test the ability to generate a proof of concept breast cancer transformation model that can be used to study transcriptional reprogramming in breast cancer and identify specific TFs that can be used as biomarkers for diagnosis, prognosis or even treatment of breast cancer. An in vitro breast cancer transformation model using HRAS overexpression in immortalized non transformednormal epithelial mammary gland cells (MCF10A) was generated. After HRAS overexpression, different cell phenotypes were tested, known to be induced by HRAS overexpression, that in order to ensure successful transformation. the transformed cells were then tested (not by us in this part of the project), for transcriptional reprogramming. Using different techniques, the model, indeed, showed massive genome wide transcriptional re-programming. Among the different transcription site activities that were lost are transcription sites of p53 and p63. In order to evaluate the role of these transcription factors in this transformation model, the functions of these two important TFs (p53 by using Nutlin-3a, and p63 by its overexpression) were reactivated. Our results, showed that the induction of these TF functions was enough to revert to certain extent some the transformation process-related phenotypes. VIn conclusion, our transformation model can be used as an efficient tool to learn about transcriptional re-programing during cellular transformation, to identify and study the role of specific TFs in transformation. This may contribute to identifying some target genes involved in breast carcinogenesis and employ them in prognosis, diagnosis and treatment

روابط وملفات

التعريف والنوع

رقم الوثيقة

08d8a9e0-47f4-4f7a-958a-48d359a50cd3

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل ماجيستير

نوع الملف

pdf text

أسماء الملفات

1696497_1.pdf

بيانات النشر

ترجمة العنوان

تصميم نموذج خلوي من أجل: دارسة آليات جديدة لإعادة برمجة النسخ الجيني في سرطان الثدي

ألقاب المؤلفين

[{"name_ar":"زيدون صلاح","title_ar":"اشراف","title_en":"Supervision"},{"name_ar":"يوسف سمير اسحق طرمان","title_ar":"اعداد","title_en":"Preparation"}]

اللغة

English

المصدر والدورية

اسم المصدر

Creating cellular model for studying novel mechanisms of transcriptional reprogramming in breast carcinogenesis

المحتوى والصفحات

عدد الصفحات

0

إشراف وإعداد

الإشراف

زيدون صلاح

الإعداد

يوسف سمير اسحق طرمان

الاقتباسات الببليوغرافية