Abstract 15P
Background
Estrogen plays a pivotal role in the development of breast cancer. Previous studies have shown that estrogen enhances cell proliferation via regulating its target gene expression in human breast cancer MCF-7 cell line. Although the effect of estrogen on the carcinogenesis in breast, the effects of pregnenolone (PG), an inactive precursor of estrogen, on MCF-7 cells or breast cancer have not been adequately explored. PG is a precursor in the biosynthesis of most of the steroid hormones containing estrogen. This investigation aimed to evaluate the effects of PG on cell proliferation and cell cycle-related protein expression.
Methods
We used Michigan Cancer Foundation-7 cell (MCF-7 cell) line, to assess the impact of PG on the carcinogenicity of breast cancer cells. We examined cell proliferation, survival rate and mobility using Bromodeoxyuridine, MTT assay and western blot. To reveal the mechanism of PG, we performed RNA seq after treatment of PG in the MCF-7 cells and transfection using siRNA of estrogen receptor and ERE luciferase vector.
Results
PG increased cell proliferation, viability, mobility, and the expression of proteins associated with the cell cycle, such as CDK2, CDK4, and Cyclin D1. We elucidated the carcinogenic mechanism of PG. Through protein-ligand docking energy analysis, we measured the affinity of PG for estrogen receptors (ERs), showing a high affinity for ERα similar to E2. When treated with cyanine 5-conjugated with PG (Cy5-PG), we observed that PG entered the cells within five minutes. Then, activated ERα entered the nucleus, bound to ERE-promoters, and significantly increased the expression of target genes associated with cell proliferation and carcinogenicity, such as pS2 and Ki-67. These results indicate that PG increases the expression of target genes through ERα and thereby affects the carcinogenicity of breast cancer cells.
Conclusions
Our results demonstrate that PG can have a significant impact on the proliferation and migration of ERα-positive breast cancer cells through ERα. Furthermore, the sustained high concentration of PG, unlike E2 which rapidly decreases after menopause, is strongly associated with the development of breast cancer. Therefore, PG has the potential to serve as a risk factor and diagnostic biomarker for breast cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
271P - Prostate cancer with histone modifier UTX mutations can benefit from olaparib
Presenter: NOBUHITO MURAMOTO
Session: Poster Display
Resources:
Abstract
272P - Comparison between MRI-targeted and standard biopsy for prostate cancer detection: A systematic review and meta-analysis
Presenter: Andree Kurniawan
Session: Poster Display
Resources:
Abstract
273P - The diagnostic performance of cognitive MRI-targeted biopsy in biopsy-naïve patients undergoing systematic 14-region 18-core biopsy: Do the three areas affect the results?
Presenter: Yuka Toyama
Session: Poster Display
Resources:
Abstract
274P - Index tumor location influencing early biochemical recurrence after radical prostatectomy in patients with negative surgical margins
Presenter: Jun Akatsuka
Session: Poster Display
Resources:
Abstract
275P - Prognosis of metastatic castration-resistant prostate cancer in response to chemotherapy and PSMA expression in circulating tumor cells
Presenter: Naoya Nagaya
Session: Poster Display
Resources:
Abstract
276P - Prognostic significance of p53 mutation in metastatic hormone-sensitive prostate cancer
Presenter: Lakshmi Kamala
Session: Poster Display
Resources:
Abstract
277P - Vasohibin-1 expression as a biomarker of aggressive growth in prostate ductal adenocarcinoma
Presenter: Murad Salomov
Session: Poster Display
Resources:
Abstract
278P - Full-coverage radiotherapy for prostate cancer patients with oligometastases
Presenter: Bichun Xu
Session: Poster Display
Resources:
Abstract
279P - Hypofractionated radiotherapy protocol implementation and early outcomes for prostate cancer patients: A single institution retrospective review
Presenter: Thu Nguyen
Session: Poster Display
Resources:
Abstract
280P - Radium-223 for patients with metastatic castration-resistant prostate cancer with symptomatic bone metastases progressing after first-line abiraterone or enzalutamide: One institutional experience
Presenter: Keng Man Chiang
Session: Poster Display
Resources:
Abstract