Related Experiment Video
Updated: May 13, 2026
10:36
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
TSPYL5 SNPs: association with plasma estradiol concentrations and aromatase expression
Mohan Liu1, James N Ingle, Brooke L Fridley
1Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA.
Molecular Endocrinology (Baltimore, Md.)
|March 23, 2013
Summary
Genetic variations near the TSPYL5 gene are linked to higher estradiol levels in postmenopausal women with ER-positive breast cancer. TSPYL5 acts as a transcription factor, regulating aromatase expression and impacting estrogen levels.
Area of Science:
- Genetics
- Endocrinology
- Oncology
Background:
- Plasma estradiol (E2) levels are crucial in postmenopausal women, particularly those with estrogen receptor (ER)-positive breast cancer.
- Understanding genetic regulation of E2 is vital for optimizing breast cancer treatment, especially concerning aromatase inhibitor therapy.
Purpose of the Study:
- To identify genetic factors influencing plasma E2 concentrations in postmenopausal women with ER-positive breast cancer.
- To elucidate the functional role of identified genetic variants in regulating E2 and aromatase expression.
Main Methods:
- Genome-wide association study (GWAS) in 772 postmenopausal women with ER-positive breast cancer.
- Functional analysis using lymphoblastoid cell lines (LCLs) and MCF-7 cells to assess TSPYL5 and aromatase (CYP19A1) expression.
- Chromatin immunoprecipitation assays to determine TSPYL5 binding to the CYP19A1 promoter.
Main Results:
- GWAS identified significant single nucleotide polymorphisms (SNPs) near TSPYL5 associated with elevated plasma E2.
- A specific SNP (rs2583506) created a functional estrogen response element, leading to increased E2-dependent TSPYL5 expression in cells with variant genotypes.
- TSPYL5 was shown to regulate CYP19A1 expression via the I.4 promoter and function as a transcription factor for multiple genes.
Conclusions:
- Novel genome-wide significant SNPs in TSPYL5 are associated with elevated plasma E2 in postmenopausal ER-positive breast cancer patients.
- TSPYL5 plays a regulatory role in aromatase expression and E2 concentrations through a newly identified mechanism.
- These findings offer insights into E2 regulation in postmenopausal women and may inform breast cancer management strategies.
Related Concept Videos
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
01:05Single Nucleotide Polymorphisms-SNPs
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
01:24Gonadal and Placental Hormones
The gonads, namely the testes in males and the ovaries in females, are pivotal in producing gonadal hormones that orchestrate the intricate processes of sexual development and reproduction.
In males, testosterone is the primary gonadal androgen. It plays a central role in the maturation of male reproductive organs — the penis and testes. Additionally, testosterone is instrumental in the development of secondary sexual characteristics — a deep voice as well as facial and pubic hair growth — and...
In males, testosterone is the primary gonadal androgen. It plays a central role in the maturation of male reproductive organs — the penis and testes. Additionally, testosterone is instrumental in the development of secondary sexual characteristics — a deep voice as well as facial and pubic hair growth — and...