Gene expression profile and cancer-associated pathways linked to progesterone receptor isoform a (PRA) predominance in transgenic mouse mammary glands
Abstract Background Progesterone receptor (PR) is expressed from a single gene as two isoforms, PRA and PRB. In normal breast human tissue, PRA and PRB are expressed in equimolar ratios, but isoform ratio is altered during malignant progression, usually leading to high PRA:PRB ratios. We took advant...
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doaj-509e9b593d644e26929e140e1dd84c712020-11-25T00:12:11ZengBMCBMC Cancer1471-24072018-06-0118111210.1186/s12885-018-4550-zGene expression profile and cancer-associated pathways linked to progesterone receptor isoform a (PRA) predominance in transgenic mouse mammary glandsMaría José Carlini0María Sol Recouvreux1Marina Simian2Maria Aparecida Nagai3Discipline of Oncology, Department of Radiology and Oncology, Faculty of Medicine, University of São PauloInstituto de Oncología “Ángel H. Roffo”Instituto de Oncología “Ángel H. Roffo”Discipline of Oncology, Department of Radiology and Oncology, Faculty of Medicine, University of São PauloAbstract Background Progesterone receptor (PR) is expressed from a single gene as two isoforms, PRA and PRB. In normal breast human tissue, PRA and PRB are expressed in equimolar ratios, but isoform ratio is altered during malignant progression, usually leading to high PRA:PRB ratios. We took advantage of a transgenic mouse model where PRA isoform is predominant (PRA transgenics) and identified the key transcriptional events and associated pathways underlying the preneoplastic phenotype in mammary glands of PRA transgenics as compared with normal wild-type littermates. Methods The transcriptomic profiles of PRA transgenics and wild-type mammary glands were generated using microarray technology. We identified differentially expressed genes and analyzed clustering, gene ontology (GO), gene set enrichment analysis (GSEA), and pathway profiles. We also performed comparisons with publicly available gene expression data sets of human breast cancer. Results We identified a large number of differentially expressed genes which were mainly associated with metabolic pathways for the PRA transgenics phenotype while inflammation- related pathways were negatively correlated. Further, we determined a significant overlap of the pathways characterizing PRA transgenics and those in breast cancer subtypes Luminal A and Luminal B and identified novel putative biomarkers, such as PDHB and LAMB3. Conclusion The transcriptional targets identified in this study should facilitate the formulation or refinement of useful molecular descriptors for diagnosis, prognosis, and therapy of breast cancer.http://link.springer.com/article/10.1186/s12885-018-4550-zProgesterone receptorIsoformsTransgenic miceMammary glandHyperplasiaBreast cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
María José Carlini María Sol Recouvreux Marina Simian Maria Aparecida Nagai |
spellingShingle |
María José Carlini María Sol Recouvreux Marina Simian Maria Aparecida Nagai Gene expression profile and cancer-associated pathways linked to progesterone receptor isoform a (PRA) predominance in transgenic mouse mammary glands BMC Cancer Progesterone receptor Isoforms Transgenic mice Mammary gland Hyperplasia Breast cancer |
author_facet |
María José Carlini María Sol Recouvreux Marina Simian Maria Aparecida Nagai |
author_sort |
María José Carlini |
title |
Gene expression profile and cancer-associated pathways linked to progesterone receptor isoform a (PRA) predominance in transgenic mouse mammary glands |
title_short |
Gene expression profile and cancer-associated pathways linked to progesterone receptor isoform a (PRA) predominance in transgenic mouse mammary glands |
title_full |
Gene expression profile and cancer-associated pathways linked to progesterone receptor isoform a (PRA) predominance in transgenic mouse mammary glands |
title_fullStr |
Gene expression profile and cancer-associated pathways linked to progesterone receptor isoform a (PRA) predominance in transgenic mouse mammary glands |
title_full_unstemmed |
Gene expression profile and cancer-associated pathways linked to progesterone receptor isoform a (PRA) predominance in transgenic mouse mammary glands |
title_sort |
gene expression profile and cancer-associated pathways linked to progesterone receptor isoform a (pra) predominance in transgenic mouse mammary glands |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2018-06-01 |
description |
Abstract Background Progesterone receptor (PR) is expressed from a single gene as two isoforms, PRA and PRB. In normal breast human tissue, PRA and PRB are expressed in equimolar ratios, but isoform ratio is altered during malignant progression, usually leading to high PRA:PRB ratios. We took advantage of a transgenic mouse model where PRA isoform is predominant (PRA transgenics) and identified the key transcriptional events and associated pathways underlying the preneoplastic phenotype in mammary glands of PRA transgenics as compared with normal wild-type littermates. Methods The transcriptomic profiles of PRA transgenics and wild-type mammary glands were generated using microarray technology. We identified differentially expressed genes and analyzed clustering, gene ontology (GO), gene set enrichment analysis (GSEA), and pathway profiles. We also performed comparisons with publicly available gene expression data sets of human breast cancer. Results We identified a large number of differentially expressed genes which were mainly associated with metabolic pathways for the PRA transgenics phenotype while inflammation- related pathways were negatively correlated. Further, we determined a significant overlap of the pathways characterizing PRA transgenics and those in breast cancer subtypes Luminal A and Luminal B and identified novel putative biomarkers, such as PDHB and LAMB3. Conclusion The transcriptional targets identified in this study should facilitate the formulation or refinement of useful molecular descriptors for diagnosis, prognosis, and therapy of breast cancer. |
topic |
Progesterone receptor Isoforms Transgenic mice Mammary gland Hyperplasia Breast cancer |
url |
http://link.springer.com/article/10.1186/s12885-018-4550-z |
work_keys_str_mv |
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