Related Experiment Video
Updated: Jul 16, 2026
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Influence of estrogens and antiestrogens on the expression of selected hormone-responsive genes
Piero Sismondi1, Nicoletta Biglia, Riccardo Ponzone
1Cattedra di Ginecologia Oncologica, Istituto per la Ricerca e la Cura del Cancro, Università Degli Studi di Torino, Candiolo, Italy. p.sismondi@tin.it
Abstract:
Estrogen exerts a primary regulatory role on a wide variety of physiological processes in different tissues and organs. Agonistic ad antagonistic compounds are widely used in human health and, therefore, a deep understanding of their mechanisms of action at the molecular level is mandatory. The effect of 17beta-estradiol and three antiestrogenic drugs, comprising two selective estrogen receptor modulator (SERM, 4-OH-tamoxifen, Raloxifene) and the pure antiestrogen ICI 182,780, on genome-wide gene expression levels was evaluated in breast carcinoma cell lines by DNA microarray analysis. Different clusters of genes, showing specific coregulation patterns, were found. First, several groups of genes displaying temporal-specific up- or down-regulation were characterized. Second, clusters of genes responding to different antiestrogenic drugs in either antagonstic or agonistic fashion, were found. Genes responding specifically to antiestrogens, but not to estrogen, were also identified. In addition, each individual compound exhibited a very specific gene regulation. Bioinformatic analysis was applied to the regulatory sequences of different groups of genes and confirmed that specific pathways and secondary responses are activated at each temporal point and in response to different compounds. Our results underline the complexity of genomic responses to estrogen in breast cancer cells and strongly suggest that the molecular characterization of estrogen agonists and antagonists used in human therapy should be carefully studied.
Insights
Estrogen compounds impact gene expression in breast cancer cells. Understanding these complex genomic responses is crucial for developing effective therapies targeting estrogen receptors.
Area of Science:
- Molecular Biology
- Genomics
- Endocrinology
Background:
- Estrogen regulates numerous physiological processes.
- Estrogen agonists and antagonists are vital in human health, necessitating molecular-level understanding of their action.
- Breast cancer cells are influenced by estrogen signaling.
Purpose of the Study:
- To investigate the genome-wide gene expression effects of 17beta-estradiol and antiestrogenic drugs in breast carcinoma cell lines.
- To identify specific gene clusters and regulatory patterns in response to estrogenic compounds.
- To elucidate the complex molecular mechanisms of estrogen action and antiestrogen activity.
Main Methods:
- DNA microarray analysis to assess genome-wide gene expression.
- Treatment of breast carcinoma cell lines with 17beta-estradiol, 4-OH-tamoxifen, Raloxifene, and ICI 182,780.
- Bioinformatic analysis of gene regulatory sequences.
Main Results:
- Identified distinct gene clusters with temporal-specific up- or down-regulation.
- Observed differential gene responses to antiestrogenic drugs, exhibiting both agonistic and antagonistic effects.
- Discovered genes uniquely responsive to antiestrogens, independent of estrogen stimulation.
- Characterized compound-specific gene regulation patterns and confirmed pathway activation via bioinformatic analysis.
Conclusions:
- Genomic responses to estrogen in breast cancer cells are highly complex.
- Different antiestrogenic drugs elicit unique and specific gene expression profiles.
- Thorough molecular characterization of therapeutic estrogen agonists and antagonists is essential for optimizing patient treatment.
More Related Videos
Related Concept Videos
01:22Target Cell Response to Hormones
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
01:31Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
01:27Major Hormones and Their Functions
Oxytocin, produced in the hypothalamus and released by the pituitary gland, plays a role in social bonding, childbirth, and lactation.
01:19Regulation of Hormone Secretion
Humoral stimuli,...
01:22Hormonal Regulation of the Menstrual Cycle
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH release.
01:24Gonadal and Placental Hormones
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...