Effects of serum estradiol and progesterone on estrogen-regulated gene expression in breast cancers of premenopausal patients

Wanifuchi‐Endo, Yumi; Asano, Tomoko; Kondo, Naoto; Hato, Yukari; Dong, Yanmei; Hisada, Tomoka; Nishikawa, Sayaka; Kato, Hiroyuki; Takahashi, Satoru; Okuda, Kunio; Yamashita, Hiroko; Toyama, Tatsuya

doi:10.1093/jjco/hyy156

Cited by 3 publications

(4 citation statements)

References 25 publications

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“…This is in agreement with a recent study which showed a correlation of GREB1 , PGR and TFF1 but not PDZK1 gene expression in ER +ve tumours with serum oestradiol levels in premenopausal patients. 32 This latter study concurred with our earlier cross-sectional study but lacked the longitudinal aspect of the current study to allow consideration of within patient changes. Overall, the AvERG showed a near twofold increase in expression between W1 and W2 or W3.…”

Section: Discussionsupporting

confidence: 85%

Menstrual cycle associated changes in hormone-related gene expression in oestrogen receptor positive breast cancer

et al. 2019

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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.

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Section: Discussionsupporting

confidence: 85%

Menstrual cycle associated changes in hormone-related gene expression in oestrogen receptor positive breast cancer

et al. 2019

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“…Total RNA was extracted from frozen breast cancer tissue sections using an RNeasy Mini Kit (Qiagen) according to the manufacturer's protocol, as described previously. RT was performed using a High-Capacity cDNA Reverse Transcription Kit (Thermo Fisher Scientific, Inc.) according to the manufacturer's protocol ( 11 ). The High-Capacity cDNA Reverse Transcription Kit included RT Buffer, RT Random Primers, dNTP Mix and MultiScribe Reverse Transcriptase.…”

Section: Methodsmentioning

confidence: 99%

“…Samples were amplified independently in duplicate. The results were converted into relative concentrations using an in-run standard curve, and then normalized to the mean values of ACTB to account for variations in the amount of input cDNA ( 11 ). The assay numbers were Hs01097169_m1 for ATP6V1A , Hs01665324_m1 for APOBEC3F , and 4333762T for ACTB (Thermo Fisher Scientific, Inc.).…”

Section: Methodsmentioning

confidence: 99%

“…Tissues were fixed by immersion in 10% neutral buffered formalin at room temperature for 24–48 h and then embedded in paraffin to prepare sections. A section (4 µm) from each paraffin-embedded specimen was first stained with hematoxylin and eosin to ascertain whether it included enough invasive ductal carcinoma cells and if the fixation quality was adequate for IHC analysis, as described previously ( 11 ). Serial sections were then prepared from suitable tissue blocks and float-mounted on adhesive-coated glass slides for the staining of estrogen receptor α (ERα), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) using the following primary antibodies: mouse monoclonal anti-human antibodies against ERα (1:100, 1D5; Dako), PgR (1:100, PgR636; Dako), and rabbit anti-human c-erbB2 oncoprotein antibody (1:200; Dako) to stain for HER2, as well as rabbit polyclonal anti-human ATP6V1A antibody (1:100, ab103445; Abcam) and rabbit polyclonal anti-human APOBEC3D+APOBEC3F antibody (1:50, ab74205; Abcam).…”

Section: Methodsmentioning

confidence: 99%

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Discovering novel mechanisms of taxane resistance in human breast cancer by whole‑exome sequencing

et al. 2021

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Taxanes are important drugs used in the treatment of breast cancer; however, some cancer types are taxane-resistant. The aim of the present study was to investigate the underlying mechanisms of taxane resistance using whole-exome sequencing (WES). Six patients with breast cancer whose tumors responded well to anthracycline treatment but grew rapidly during neoadjuvant taxane-based chemotherapy, were included in the present study. WES of samples from these patients was carried out to identify somatic mutations of candidate genes thought to affect taxane resistance, and the candidate proteins were structurally modeled. The mRNA and protein expression levels of these candidate genes in other breast cancers treated with taxanes were also examined. Nine variants common to all six patients were identified and two of these [R552P in V-type proton ATPase catalytic subunit A ( ATP6V1A ) and T114P in apolipoprotein B MRNA editing enzyme catalytic subunit 3F ( APOBEC3F )] were selected. The results also showed that, protein-structure visualization suggested that these mutations may cause structural changes. The Kaplan-Meier analyses revealed that higher APT6V1A and APOBEC3F expression levels were significantly associated with poorer disease-free survival (DFS) and overall survival. Moreover, multivariate analysis identified high ATP6V1A mRNA expression as an independent risk factor for poor DFS. Two specific mutations that might affect taxane resistance were identified. Thus, these results suggest that breast cancer patients receiving taxanes who have high ATP6V1A or APOBEC3F expression levels may have shorter survival.

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The menstrual cycle is an under-appreciated factor in premenopausal breast cancer diagnosis and treatment

Bernhardt

Dasari

Walsh

et al. 2020

Current Opinion in Endocrine and Metabolic Research

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Effects of serum estradiol and progesterone on estrogen-regulated gene expression in breast cancers of premenopausal patients

Cited by 3 publications

References 25 publications

Menstrual cycle associated changes in hormone-related gene expression in oestrogen receptor positive breast cancer

Menstrual cycle associated changes in hormone-related gene expression in oestrogen receptor positive breast cancer

Discovering novel mechanisms of taxane resistance in human breast cancer by whole‑exome sequencing

The menstrual cycle is an under-appreciated factor in premenopausal breast cancer diagnosis and treatment

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