# Research Project-1: Midasin, A Novel Biomarker for Endocrine Resistant Breast Cancer > **NIH NIH U54** · FLORIDA AGRICULTURAL AND MECHANICAL UNIV · 2024 · $210,460 ## Abstract Project-1 Summary/Abstract: Although mortality rates for estrogen receptor-positive breast cancer in the US have been rapidly declining with the onset of successful endocrine therapy [i.e., aromatase inhibitors (AI) and selective estrogen receptor modulators] and targeted therapy (ie., cdk 4/6 inhibitors), the development of re- sistance remains a lingering clinical challenge. Unfortunately, once resistance develops, the tumors spread and become estrogen-independent, thereby limiting favorable therapeutic outcomes. The long-term goal is to better understand the mechanism(s) of AI-resistant breast cancer, in order to contribute to both the improvement of current therapeutic modalities and the development of novel treatment strategies. The objective of this applica- tion is to define the functional relevance and consequence of midasin expression in the endocrine resistant setting. The central hypothesis of the proposed research is that overexpression of midasin poises cells for en- docrine resistance by increasing plasticity, cell cycle dysregulation, genomic instability, and reprogramming the transcriptional landscape. The rationale for the proposed project is that defining the relationship between aber- rant midasin expression and AI-resistance could aid in the discovery new pathways to restore sensitivity to re- sistant tumors. Guided by strong preliminary data, this hypothesis will be tested by pursuing three specific aims: 1) To elucidate the impact of midasin expression on stemness of letrozole-resistant breast cancer; 2) To deter- mine the consequence of midasin alterations on cell cycle dysregulation and genomic instability; and 3) To in- terrogate the role of ESR1 mutations and midasin alterations in promoting a more aggressive phenotype. Under the first aim, we will use 2D and 3D tissue cell culture to analyze CSC formation, proliferation, motility, metastasis, and its resultant biology in letrozole-sensitive and letrozole-resistant breast cancer cells in vitro and in vivo in which midasin has been genetically and pharmacologically. Under the second aim, we will alter midasin expres- sion in letrozole-sensitive and letrozole-resistant breast cancer cells containing targeting vectors with empty, over-expressed, and/or knocked down midasin and analyze cell proliferation, cell cycle progression, DNA dam- age, and apoptosis and its resultant biology. Under the third aim, MCF-7 cells containing stable point mutations in the ER LBD and measure ER transcriptional activity, recruitment of p160 coactivators, and its subsequent biology upon genetic and pharmacological midasin manipulation. The proposed research is conceptually inno- vative, because dissecting the consequences of aberrant midasin expression will uncover key pathways that may be instrumental in selectively targeting this phenotype and ultimately restoring hormone sensitivity of endo- crine breast cancer. This is proposed research is significant because it will elucidate the impact of... ## Key facts - **NIH application ID:** 11001306 - **Project number:** 2U54MD007582-39 - **Recipient organization:** FLORIDA AGRICULTURAL AND MECHANICAL UNIV - **Principal Investigator:** Syreeta L Tilghman - **Activity code:** U54 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $210,460 - **Award type:** 2 - **Project period:** 1997-08-01 → 2029-03-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/11001306 ## Citation > US National Institutes of Health, RePORTER application 11001306, Research Project-1: Midasin, A Novel Biomarker for Endocrine Resistant Breast Cancer (2U54MD007582-39). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11001306. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*