Dataset Information

Loss of progesterone receptor is associated with distinct tyrosine kinase profiles in breast cancer.

ABSTRACT: PURPOSE:The aim of this study was to assess protein tyrosine kinase profiles in primary breast cancer samples in correlation with the distinct hormone and growth receptor profiles ER, PR, and HER2. EXPERIMENTAL DESIGN:Pamchip® microarrays were used to measure the phosphorylation of 144 tyrosine kinase substrates in 29 ER+?breast cancer samples and cell lines MCF7, BT474 and ZR75-1. mRNA expression data from the METABRIC cohort and publicly available PR chip-sequencing data were used for validation purposes, together with RT-PCR. RESULTS:In ER+ breast tumors and cell lines, we observed that the loss of PR expression correlated to higher kinase activity in samples and cell lines that were HER2-. A number of kinases, representing mostly proteins within the PI3K/AKT pathway, were identified as responsible for the differential phosphorylation between PR- and PR+ in ER+/HER2- tumors. We used the METABRIC cohort to analyze mRNA expression from 977 ER+/HER2- breast cancers. Twenty four kinase-encoding genes were identified as differentially expressed between PR+ and PR-, dividing ER+/HER2- samples in two distinct clusters with significant differences in survival (p?

SUBMITTER: Tahiri A

PROVIDER: S-EPMC7497693 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Loss of progesterone receptor is associated with distinct tyrosine kinase profiles in breast cancer.

Tahiri Andliena A Tekpli Xavier X Satheesh Somisetty V SV DeWijn Rik R Lüders Torben T Bukholm Ida R IR Hurtado Antoni A Geisler Jürgen J Kristensen Vessela N VN

Breast cancer research and treatment 20200724 3

<h4>Purpose</h4>The aim of this study was to assess protein tyrosine kinase profiles in primary breast cancer samples in correlation with the distinct hormone and growth receptor profiles ER, PR, and HER2.<h4>Experimental design</h4>Pamchip® microarrays were used to measure the phosphorylation of 144 tyrosine kinase substrates in 29 ER+ breast cancer samples and cell lines MCF7, BT474 and ZR75-1. mRNA expression data from the METABRIC cohort and publicly available PR chip-sequencing data were us ...[more]

PMID: 32710281

Similar Datasets

Project description:Simple Summary Most breast cancers co-express estrogen receptor α (ERα) and progesterone receptor (PgR). These cancers are sensitive to endocrine therapy and, in general, have superior outcomes. However, a subset of tumors expresses ERα but loses expression of PgR in various mechanisms. The processes driving the loss of PgR may cause resistance to hormonal treatment and a more aggressive clinical course. The current review summarizes current knowledge on the biology of ERα-positive PgR(−)negative breast cancer and discusses the associations between molecular mechanisms and clinical characteristics. Abstract Estrogen receptor α (ERα) and progesterone receptor (PgR) are crucial prognostic and predictive biomarkers that are usually co-expressed in breast cancer (BC). However, 12–24% of BCs present ERα(+)/PgR(−) phenotype at immunohistochemical evaluation. In fact, BC may either show primary PgR(−) status (in chemonaïve tumor sample), lose PgR expression during neoadjuvant treatment, or acquire PgR(−) phenotype in local relapse or metastasis. The loss of PgR expression in ERα(+) breast cancer may signify resistance to endocrine therapy and poorer outcomes. On the other hand, ERα(+)/PgR(−) BCs may have a better response to neoadjuvant chemotherapy than double-positive tumors. Loss of PgR expression may be a result of pre-transcriptional alterations (copy number loss, mutation, epigenetic modifications), decreased transcription of the PGR gene (e.g., by microRNAs), and post-translational modifications (e.g., phosphorylation, sumoylation). Various processes involved in the down-regulation of PgR have distinct consequences on the biology of cancer cells. Occasionally, negative PgR status detected by immunohistochemical analysis is paradoxically associated with enhanced transcriptional activity of PgR that might be inhibited by antiprogestin treatment. Identification of the mechanism of PgR loss in each patient seems challenging, yet it may provide important information on the biology of the tumor and predict its responsiveness to the therapy.

Dataset Information

Loss of progesterone receptor is associated with distinct tyrosine kinase profiles in breast cancer.

Publications

Loss of progesterone receptor is associated with distinct tyrosine kinase profiles in breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets