Summary of project PR001260
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001260. The data can be accessed directly via it's Project DOI: 10.21228/M8V401 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001260 |
| Project DOI: | doi: 10.21228/M8V401 |
| Project Title: | Metabolic adaptations in an endocrine-related breast cancer mouse model unveil potential markers of tumor response to hormonal therapy |
| Project Type: | NMR spectra |
| Project Summary: | Breast cancer (BC) is the most common type of cancer in women and, in most cases, it is hormone-dependent (HD), thus relying on ovarian hormone activation of intracellular receptors to stimulate tumor growth. Endocrine therapy (ET) aimed at preventing hormone receptor activation is the primary treatment strategy, however, about half of the patients, develop resistance in time. This involves the development of hormone independent tumors that initially are ET-responsive (HI), which may subsequently become resistant (HIR). The mechanisms that promote the conversion of HI to HIR tumors are varied and not completely understood. The aim of this work was to characterize the metabolic adaptations accompanying this conversion through the analysis of the polar metabolomes of tumor tissue and non-compromised mammary gland from mice implanted subcutaneously with HD, HI and HIR tumors from a medroxyprogesterone acetate (MPA)-induced BC mouse model. This was carried out by nuclear magnetic resonance (NMR) spectroscopy of tissue polar extracts and data mining through multivariate and univariate statistical analysis. Initial results unveiled marked changes between global tumor profiles and non-compromised mammary gland tissues, as expected. More importantly, specific metabolic signatures were found to accompany progression from HD, through HI and to HIR tumors, impacting on amino acids, nucleotides, membrane percursors and metabolites related to oxidative stress protection mechanisms. For each transition, sets of polar metabolites are advanced as potential markers of progression, including acquisition of resistance to ET. Putative biochemical interpretation of such signatures are proposed and discussed. |
| Institute: | University of Aveiro |
| Department: | Chemistry |
| Laboratory: | Metabolomics |
| Last Name: | Araújo |
| First Name: | Rita |
| Address: | Campus Universitário de Santiago, 3810-193, Aveiro, Portugal |
| Email: | anarita.asilva@ua.pt |
| Phone: | 913355325 |
| Funding Source: | This work was developed within the scope of the project CICECO Aveiro Institute of Materials, UIDB/50011/2020 and UIDP/50011/2020, financed by national funds through the FCT/MCTE and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. AMG acknowledges the Portuguese National NMR Network (RNRMN), supported by FCT funds, and RA thanks RNRMN for her grant through the Doctoral Program in NMR applied to Chemistry, Materials and Biosciences – PTNMRPhD (PD/00065/2013). The authors also acknowledge financial support from the Portuguese Foundation for Science and Technology through projects UIDB/04501/2020, UIDP/04501/2020, MEDISIS (CENTRO-01-0246-FEDER-000018) and pAGE (CENTRO-01-0145-FEDER-000003) project cofounded through the Comissão de Coordenação e Desenvolvimento Regional do Centro and COMPETE 2020 program and European Union fund FEDER (L.H.). The authors also acknowledge the Agencia Nacional de Promoción Científica y Tecnológica, Argentina (ANPCYT); grant PICT 2017-2073 (C.L.). |
Summary of all studies in project PR001260
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST001984 | Metabolic adaptations in an endocrine-related breast cancer mouse model unveil potential markers of tumor response to hormonal therapy | Mus musculus | University of Aveiro | NMR | 2021-12-01 | 1 | 66 | Not available |
