Evidence map›Paper›PMID 35267540›Full record

ArticleCancers2022

Matrix Metalloproteinase-1 (MMP1) Upregulation through Promoter Hypomethylation Enhances Tamoxifen Resistance in Breast Cancer.

Hyeon Woo Kim, Jae Eun Park, Minjae Baek, Heejoo Kim, Hwee Won Ji, Sung Hwan Yun, Dawoon Jeong, Juyeon Ham, Sungbin Park, Xinpei Lu and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.3field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 35 citations in OpenAlex.

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  17. The Mechanism of DNA Methylation and miRNA in Breast Cancer.International journal of molecular sciences · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Hyeon Woo KimDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Korea.ORCID 0000-0002-8951-6008
Jae Eun ParkDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Korea.
Minjae BaekDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Korea.
Heejoo KimDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Korea.
Hwee Won JiDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Korea.
Sung Hwan YunDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Korea.
Dawoon JeongDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Korea.
Juyeon HamDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Korea.
Sungbin ParkDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Korea.
Xinpei LuState Key Laboratory of Advanced Electromagnetic Engineering and Technology, School of Electrical and Electronic Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.
Han-Sung KangResearch Institute and Hospital, National Cancer Center, Goyang 10408, Korea.
Sun Jung KimDepartment of Life Science, Dongguk University-Seoul, Goyang 10326, Korea.ORCID 0000-0001-6818-3956
Dongguk University · KRHuazhong University of Science and Technology · CNNational Cancer Center · KR

Funding

National Research Foundation of Korea NRF-2016R1D1A1B01009235
6 · The paper itself

Abstract

backgroundTamoxifen (tam) is widely used to treat estrogen-positive breast cancer. However, cancer recurrence after chemotherapy remains a major obstacle to achieve good patient prognoses. In this study, we aimed to identify genes responsible for epigenetic regulation of tam resistance in breast cancer.

methodsMethylation microarray data were analyzed to screen highly hypomethylated genes in tam resistant (tamR) breast cancer cells. Quantitative RT-PCR, Western blot analysis, and immunohistochemical staining were used to quantify expression levels of genes in cultured cells and cancer tissues. Effects of matrix metalloproteinase-1 (MMP1) expression on cancer cell growth and drug resistance were examined through colony formation assays and flow cytometry. Xenografted mice were generated to investigate the effects of MMP1 on drug resistance in vivo.

resultsMMP1 was found to be hypomethylated and overexpressed in tamR MCF-7 (MCF-7/tamR) cells and in tamR breast cancer tissues. Methylation was found to be inversely associated with MMP1 expression level in breast cancer tissues, and patients with lower MMP1 expression exhibited a better prognosis for survival. Downregulating MMP1 using shRNA induced tam sensitivity in MCF-7/tamR cells along with increased apoptosis. The xenografted MCF-7/tamR cells that stably expressed short hairpin RNA (shRNA) against MMP1 exhibited retarded tumor growth compared to that in cells expressing the control shRNA, which was further suppressed by tam.

conclusionsMMP1 can be upregulated through promoter hypomethylation in tamR breast cancer, functioning as a resistance driver gene. MMP1 can be a potential target to suppress tamR to achieve better prognoses of breast cancer patients.

Indexed as

breast cancerCpG methylationMMP1tamoxifen resistancexenograft

Identifiers

PMID35267540
PMCPMC8909089
OpenAlexW4214713581

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.