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
298P - Managing locally advanced cervical cancer: Insights from a tertiary care center and a 3-year follow-up on outcomes
Presenter: Ambedkar Yadala
Session: Poster Display
Resources:
Abstract
299P - Sexual dysfunction assessment in longterm survivors of carcinoma cervix using LENT SOMA scale
Presenter: Niharika Sethi
Session: Poster Display
Resources:
Abstract
300P - Assessing ovarian function in Vietnamese cervical cancer patients who underwent ovary transposition prior to pelvic radiation therapy
Presenter: Cuong Nguyen
Session: Poster Display
Resources:
Abstract
301P - Correlation between cervical cancer recurrence after radiation therapy and vaginal microbiome
Presenter: Xiaoxian Xu
Session: Poster Display
Resources:
Abstract
302P - Expression of ERCC4 gene and its correlation with clinical and pathological parameters in cervical cancer
Presenter: Himanshu Mishra
Session: Poster Display
Resources:
Abstract
303P - Prognostic value of body composition and systemic inflammatory markers in patients with locally advanced cervical cancer following chemoradiotherapy
Presenter: Hui Guo
Session: Poster Display
Resources:
Abstract
305P - A real-world multicenter cohort study of lenvatinib (LEN) plus pembrolizumab (PEM) in Japanese patients with endometrial cancer: Interim analysis of GOGO-EM4 study
Presenter: Yoshikazu Nagase
Session: Poster Display
Resources:
Abstract
306P - Adjuvant treatment and impact on relapse in stage IA uterine papillary serous and clear cell carcinomas: A single center retrospective study
Presenter: Sachin Khurana
Session: Poster Display
Resources:
Abstract
307P - Hormonal therapy vs combination chemotherapy in metastatic leiomyosarcomas: A systematic review
Presenter: Patricia Angel
Session: Poster Display
Resources:
Abstract
309P - Expression of estrogen receptor is a negative predictive biomarker for immunotherapy with lenvatinib plus pembrolizumab for advanced endometrial cancer with pMMR
Presenter: Hiroyuki Fujii
Session: Poster Display
Resources:
Abstract