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Crumbs protein homolog 3 (CRB3) expression is associated with oestrogen and progesterone receptor positivity in breast cancer.

ABSTRACT: The crumbs protein homolog 3 (CRB3) regulates the tight junction to help maintain epithelial polarity. Altered CRB3 expression was associated with carcinogenesis of epithelial cells. This study detected CRB3 expression in 192 cases of breast cancer tissues and in the Molecular Taxonomy of Breast Cancer International Consortium (Metabric) and The Cancer Genome Atlas (TCGA) datasets for association with triple negative breast cancer (TNBC) phenotypes. The in vitro experiments confirm the ex vivo data. The data showed that levels of both CRB3 mRNA and protein were associated with TNBC phenotypes, ie, 41.1% (39/95) of ER+ breast cancer was CRB3-positive, whereas 26.9% (25/93) ER- tumour was CRB3-positive (P = 0.046). Moreover, 47.6% (30/63) of PR+ breast cancer was CRB3-positive vs 28.4% (33/116) PR- tumours positive for CRB3 (P = 0.013). In addition, 40.1% (27/66) of ER+/PR+ tumour was CRB3-positive, but only 22.4% (19/85) of TNBC showed CRB3 expression (P = 0.048). Indeed, levels of CRB3 mRNA were higher in non-TNBC than TNBC in both Metabric (P = 3.682e-10) and TCGA datasets (P = 2.501e-07). The in vitro data showed that CRB3 expression was higher in luminal (MCF7 and T47D) than in HER2 (MDA-MB-453 and SK-BR-3) and basal (MDA-MB-231 and BT-549) breast cancer cell lines. More interestingly, ER? regulated expression of CRB3 protein in MCF7 and BT-549 cells and ER? expression was associated with CRB3 expression in breast cancer tissues specimens. This study demonstrated that ER? could be a novel regulator for CRB3 expression in breast cancer.

SUBMITTER: Li P

PROVIDER: S-EPMC6772053 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Crumbs protein homolog 3 (CRB3) expression is associated with oestrogen and progesterone receptor positivity in breast cancer.

Li Pingping P Zhou Can C Yan Yu Y Li Juan J Liu Jie J Zhang Yan Y Liu Peijun P

Clinical and experimental pharmacology & physiology 20190610 9

The crumbs protein homolog 3 (CRB3) regulates the tight junction to help maintain epithelial polarity. Altered CRB3 expression was associated with carcinogenesis of epithelial cells. This study detected CRB3 expression in 192 cases of breast cancer tissues and in the Molecular Taxonomy of Breast Cancer International Consortium (Metabric) and The Cancer Genome Atlas (TCGA) datasets for association with triple negative breast cancer (TNBC) phenotypes. The in vitro experiments confirm the ex vivo d ...[more]

PMID: 31087799

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Project description:IntroductionBreast cancer is a heterogeneous disease encompassing a number of phenotypically diverse tumours. Expression levels of the oestrogen, progesterone and HER2/neu receptors which characterize clinically distinct breast tumours have been shown to change during disease progression and in response to systemic therapies. Mi(cro)RNAs play critical roles in diverse biological processes and are aberrantly expressed in several human neoplasms including breast cancer, where they function as regulators of tumour behaviour and progression. The aims of this study were to identify miRNA signatures that accurately predict the oestrogen receptor (ER), progesterone receptor (PR) and HER2/neu receptor status of breast cancer patients to provide insight into the regulation of breast cancer phenotypes and progression.MethodsExpression profiling of 453 miRNAs was performed in 29 early-stage breast cancer specimens. miRNA signatures associated with ER, PR and HER2/neu status were generated using artificial neural networks (ANN), and expression of specific miRNAs was validated using RQ-PCR.ResultsStepwise ANN analysis identified predictive miRNA signatures corresponding with oestrogen (miR-342, miR-299, miR-217, miR-190, miR-135b, miR-218), progesterone (miR-520g, miR-377, miR-527-518a, miR-520f-520c) and HER2/neu (miR-520d, miR-181c, miR-302c, miR-376b, miR-30e) receptor status. MiR-342 and miR-520g expression was further analysed in 95 breast tumours. MiR-342 expression was highest in ER and HER2/neu-positive luminal B tumours and lowest in triple-negative tumours. MiR-520g expression was elevated in ER and PR-negative tumours.ConclusionsThis study demonstrates that ANN analysis reliably identifies biologically relevant miRNAs associated with specific breast cancer phenotypes. The association of specific miRNAs with ER, PR and HER2/neu status indicates a role for these miRNAs in disease classification of breast cancer. Decreased expression of miR-342 in the therapeutically challenging triple-negative breast tumours, increased miR-342 expression in the luminal B tumours, and downregulated miR-520g in ER and PR-positive tumours indicates that not only is dysregulated miRNA expression a marker for poorer prognosis breast cancer, but that it could also present an attractive target for therapeutic intervention.

Project description:The major changes in hormone levels that occur through the menstrual cycle have been postulated to affect the expression of hormone-regulated and proliferation-associated genes (PAGs) in premenopausal ER+ breast cancer. Whilst previous studies have demonstrated differences in gene expression, here, we investigated if there are within patient changes in the expression of oestrogen- and progesterone-regulated genes (ERGs and PRGs) and PAGs in ER+ breast cancer during the menstrual cycle. Samples from 96 patients in two independent prospective studies of the effect of menstrual cycle on ER+ breast cancer were used. Plasma hormone measurements were used to assign tumours to one of three pre-defined menstrual cycle windows: W1 (days 27-35 and 1-6; low oestradiol and low progesterone), W2 (days 7-16; high oestradiol and low progesterone) and W3 (days 17-26; intermediate oestradiol and high progesterone). RNA expression of 50 genes, including 27 ERGs, 11 putative PRGs and seven PAGs was measured. The AvERG (geomean of PGR, GREB1, TFF1 and PDZK1) was used as a composite measure of ERG expression and showed significant changes between the three windows of the menstrual cycle increasing over 2.2-fold between W1 and W2 and decreasing between W2 and W3 and between W3 and W1. Proliferation gene expression also varied significantly, following the same pattern of changes as ERG expression, but the changes were of lower magnitude (1.4-fold increase between W1 and W2). Significant changes in the expression of eight individual ERGs, including GREB1, PGR and TFF1, and two PAGs were observed between W1 and either W2 or W3 with all genes showing higher levels in W2 or W3 (1.3-2.4-fold; FDR 0.016-0.05). The AvProg, a composite measure of PRG expression, increased significantly (1.5-fold) in W3 compared to W1 or W2 but no significant changes were observed for individual PRGs. In conclusion, we observed significant changes in ERG, PRG and PAG expression in ER+ breast tumours during the menstrual cycle that may affect the assessment and interpretation of prominent biomarkers (e.g. PgR) and commonly used multigene prognostic signatures in premenopausal ER+ breast cancer.

Dataset Information

Crumbs protein homolog 3 (CRB3) expression is associated with oestrogen and progesterone receptor positivity in breast cancer.

Publications

Crumbs protein homolog 3 (CRB3) expression is associated with oestrogen and progesterone receptor positivity in breast cancer.

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