Involvement of RFC3 in tamoxifen resistance in ER-positive breast cancer through the cell cycle
Open accessAbstract
Since the establishment of the molecular subtyping system, ER positive breast cancer was considered to be the most prevalent type of breast cancer, and endocrine therapy was a very important solution. However, numerous studies have shown that the cell cycle plays a key role in the progression and metastasis of breast cancer. The present study showed that RFC3 was involved in the cell cycle through DNA replication. Furthermore, RFC3 expression was significantly higher in breast cancer-resistant cells than in parental cells, which correlated with the cell cycle. We confirmed these results by established drug-resistant cell lines for breast cancer, raw letter analysis and immunohistochemical analysis of primary and recurrent tissues from three ER+ breast cancers. In addition, analysis of the results through an online database revealed that RFC3 expression was significantly associated with poor prognosis in ER+ breast cancer. We also demonstrated that in ER positive breast cancer-resistant cells, knockdown of RFC3 blocked the S-phase of cells and significantly attenuated cell proliferation, migration and invasion. Furthermore, RFC3 overexpression in ER positive breast cancer cells enhanced cell proliferation, migration and invasion. Taking all these findings into account, we could conclude that RFC3 was involved in endocrine resistance in breast cancer through the cell cycle. Thus, RFC3 may be a target to address endocrine therapy resistance in ER positive breast cancer and may be an independent prognostic factor in ER positive breast cancer.
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Tamoxifen remains the standard first-line treatment for ER-positive breast cancer and has significantly improved patient prognosis.
“Although Tamoxifen remains the standard first-line treatment for ER-positive breast cancer and has significantly improved patient prognosis”
From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [57]
The Introduction states that clinical use of tamoxifen has brought significant prognostic improvements in patients with estrogen-positive breast cancer. It describes tamoxifen as a treatment for hormone-dependent breast cancer, but does not say it remains the standard first-line treatment. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDevelopment of acquired resistance to Tamoxifen continues to pose a major clinical challenge.
“the development of acquired resistance continues to pose a major clinical challenge57.”
From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [57]
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- Authors
- Zhu, J., Ye, L., Sun, S., Yuan, J., Huang, J., & Zeng, Z.
- Affiliations
- Department of Breast, Foshan Fosun Chancheng Hospital, Foshan, Guangdong, China
- Guangzhou University of Chinese Medicine (CN)
- Department of General Surgery, Foshan Fosun Chancheng Hospital, Foshan, Guangdong, China
- Corresponding author
- Zeng, Zhiqiang
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2023-12-06
- Volume
- 15
- Issue
- 23
- Pages
- 13738-13752
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC10756131
- OpenAlex
- W4389420612
- Cited by
- 10
- References
- 37
- Citations by year
- 2026: 1 · 2025: 9
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Aging (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
- Keywords
- tamoxifen resistance, estrogen receptor-positive breast cancer, endocrine therapy resistance, cell cycle, DNA replication, S phase, cell proliferation, cell migration and invasion, prognostic factors, drug resistance
- MeSH terms
- Breast Neoplasms, Cell Cycle, Cell Division, Female, Humans, Tamoxifen, Drug Resistance, Neoplasm, Cell Line, Tumor, Cell Proliferation, Replication Protein C
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