ArticleDevelopmental biology2012
The estrogen-responsive Agr2 gene regulates mammary epithelial proliferation and facilitates lobuloalveolar development.
Article in Developmental biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 53 citations in OpenAlex.
- Article
- AGR2: The Covert Driver and New Dawn of Hepatobiliary and Pancreatic Cancer Treatment.Biomolecules · 2024Review
- The Lineage Differentiation and Dynamic Heterogeneity of Thymic Epithelial Cells During Thymus Organogenesis.Frontiers in immunology · 2022Article
- MicroRNAs as the critical regulators of Doxorubicin resistance in breast tumor cells.Cancer cell international · 2021Review
- Effects of ER-resident and secreted AGR2 on cell proliferation, migration, invasion, and survival in PANC-1 pancreatic cancer cells.BMC cancer · 2021Article
- From development to cancer - an ever-increasing role of AGR2.American journal of cancer research · 2021Review
- Nuclear Mechanisms Involved in Endocrine Resistance.Frontiers in oncology · 2021Review
- Secretion of pro-oncogenic AGR2 protein in cancer.Heliyon · 2020Review
- AGR3 promotes estrogen receptor-positive breast cancer cell proliferation in an estrogen-dependent manner.Oncology letters · 2020Article
- miR-135b-5p enhances doxorubicin-sensitivity of breast cancer cells through targeting anterior gradient 2.Journal of experimental & clinical cancer research : CR · 2019Article
- FOXA1 is Prognostic of Triple Negative Breast Cancers by Transcriptionally SuppressingInternational journal of biological sciences · 2019Article
- Article
- Association of increased primary breast tumorOncotarget · 2018Article
- Proteomic analysis identifies highly expressed plasma membrane proteins for detection and therapeutic targeting of specific breast cancer subtypes.Clinical proteomics · 2018Article
- The metastasis-inducing protein AGR2 is O-glycosylated upon secretion from mammary epithelial cells.Molecular and cellular biochemistry · 2015Article
- Anterior gradient protein 3 is associated with less aggressive tumors and better outcome of breast cancer patients.OncoTargets and therapy · 2015Article
- Delineation of a FOXA1/ERα/AGR2 regulatory loop that is dysregulated in endocrine therapy-resistant breast cancer.Molecular cancer research : MCR · 2014Article
- Knockdown of anterior gradient 2 expression extenuates tumor-associated phenotypes of SNU-478 ampulla of Vater cancer cells.BMC cancer · 2014Article
- Molecular response of the axillary lymph node microenvironment to metastatic colonization.Clinical & experimental metastasis · 2014Article
- Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Agr2 is a putative protein disulfide isomerase (PDI) initially identified as an estrogen-responsive gene in breast cancer cell lines. While Agr2 expression in breast cancer is positively correlated with estrogen receptor (ER) expression, it is upregulated in both hormone dependent and independent carcinomas. Several in vitro and xenograft studies have implicated Agr2 in different oncogenic features of breast cancer; however, the physiological role of Agr2 in normal mammary gland development remains to be defined. Agr2 expression is developmentally regulated in the mammary gland, with maximum expression during late pregnancy and lactation. Using a mammary gland specific knockout mouse model, we show that Agr2 facilitates normal lobuloalveolar development by regulating mammary epithelial cell proliferation; we found no effects on apoptosis in Agr2(-/-) mammary epithelial cells. Consequently, mammary glands of Agr2(-/-) females exhibit reduced expression of milk proteins, and by two weeks post-partum their pups are smaller in size. Utilizing a conditional mouse model, we show that Agr2 constitutive expression drives precocious lobuloalveolar development and increased milk protein expression in the virgin mammary gland. In vitro studies using knock down and overexpression strategies in estrogen receptor positive and negative mammary epithelial cell lines demonstrate a role for Agr2 in estradiol-induced cell proliferation. In conclusion, the estrogen-responsive Agr2, a candidate breast cancer oncogene, regulates epithelial cell proliferation and lobuloalveolar development in the mammary gland. The pro-proliferative effects of Agr2 may explain its actions in early tumorigenesis.
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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.