Estrogen stimulates cell proliferation in breast cancer. The biological effects of estrogen are mediated through two intracellular receptors, estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta). However, the role of ERs in the proliferative action of estrogen is not well established. Recently, it has been known that ER activates phosphatidylinositol-3-OH kinase (PI3K) through binding with the p85 regulatory subunit of PI3K. Therefore, possible mechanisms may include ER-mediated phosphoinositide metabolism with subsequent formation of phosphatidylinositol-3,4,5-trisphosphate (PIP(3)), which is generated from phosphatidylinositol 4,5-bisphosphate via PI3K activation. The present study demonstrates that 17beta-estradiol (E2) up-regulates PI3K in an ERalpha-dependent manner, but not ERbeta, and stimulates cell growth in breast cancer cells. In order to study this phenomenon, we have treated ERalpha-positive MCF-7 cells and ERalpha-negative MDA-MB-231 cells with 10nM E2. Treatment of MCF-7 cells with E2 resulted in a marked increase in PI3K (p85) expression, which paralleled an increase in phospho-Akt (Ser-473) and PIP(3) level. These observations also correlated with an increased activity to E2-induced cell proliferation. However, these effects of E2 on breast cancer cells were not observed in the MDA-MB-231 cell line, indicating that the E2-mediated up-regulation of PI3K/Akt pathway is ERalpha-dependent. These results suggest that estrogen activates PI3K/Akt signaling through ERalpha-dependent mechanism in MCF-7 cells.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2005.08.256DOI Listing

Publication Analysis

Top Keywords

breast cancer
16
stimulates cell
12
cancer cells
12
mcf-7 cells
12
up-regulation pi3k/akt
8
pi3k/akt signaling
8
estrogen
8
estrogen receptor-alpha
8
estrogen receptor-beta
8
cell growth
8

Similar Publications

Background: Screening of asymptomatic stage IV breast cancer with brain MRIs is currently not recommended by National Comprehensive Cancer Network (NCCN) Guidelines. The incidence of asymptomatic brain metastasis is not well documented.

Methods: The study is designed as a single arm, phase II trial, with the goal of investigating surveillance brain MRIs in neurologically asymptomatic patients with metastatic breast cancer.

View Article and Find Full Text PDF

Today, cancer has become one of the leading global tragedies. It occurs when a small number of cells in the body mutate, causing some of them to evade the body's immune system and proliferate uncontrollably. Even more irritating is the fact that patients with cancers frequently relapse after conventional chemotherapy and radiotherapy, leading to additional suffering.

View Article and Find Full Text PDF

Background: Colon adenocarcinoma (COAD) is a malignancy with a high mortality rate and complex biological characteristics and heterogeneity, which poses challenges for clinical treatment. Anoikis is a type of programmed cell death that occurs when cells lose their attachment to the extracellular matrix (ECM), and it plays a crucial role in tumor metastasis. However, the specific biological link between anoikis and COAD, as well as its mechanisms in tumor progression, remains unclear, making it a potential new direction for therapeutic strategy research.

View Article and Find Full Text PDF

Introduction: Oncolytic herpes simplex viruses (oHSVs) are a type of biotherapeutic utilized in cancer therapy due to their ability to selectively infect and destroy tumor cells without harming healthy cells. We sought to investigate the functional genomic response and altered metabolic pathways of human cancer cells to oHSV-1 infection and to elucidate the influence of these responses on the relationship between the virus and the cancer cells.

Methods: Two datasets containing gene expression profiles of tumor cells infected with oHSV-1 (G207) and non-infected cells from the Gene Expression Omnibus (GEO) database were processed and normalized using the R software.

View Article and Find Full Text PDF

Background: Breast cancer remains a leading cause of mortality among women, driven by the molecular complexity of its various subtypes. This study aimed to investigate the differential expression of genes and miRNAs involved in the PI3K/AKT/mTOR signaling pathway, a critical regulator of cancer progression.

Methods: We analyzed tumor tissues from five breast cancer subtypes-luminal A, luminal B HER2-negative, luminal B HER2-positive, HER2-positive, and triple-negative breast cancer (TNBC)-and compared them with non-cancerous tissues.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!