Journal of Mammary Gland Biology and Neoplasia最新文献

{"title":"Transcription Impairment of TMEM208 by ZBTB14 Suppresses Breast cancer Radiotherapy Resistance.","authors":"Yan Li, Lili Liang","doi":"10.1007/s10911-024-09573-1","DOIUrl":"10.1007/s10911-024-09573-1","url":null,"abstract":"<p><p>Zinc finger and BTB domain-containing protein (ZBTB) proteins have been implicated in different cellular processes, including DNA damage responses and cell cycle progression. However, the mechanism by which ZBTB14 modulates radiotherapy (RT) radioresistance (RT-R) remains to be elucidated. We aimed to elucidate the regulation mechanism of ZBTB14 in breast cancer (BC) RT-R. Using integrated bioinformatics prediction, ZBTB14 was identified as a hub transcription factor related to RT-R in BC. ZBTB14 was significantly under-expressed in non-responders and RT-R/BC cells, whereas its target transmembrane protein 208 (TMEM208) was significantly overexpressed in non-responders and RT-R/BC cells. Chromatin immunoprecipitation-qPCR and luciferase reporter assays revealed that ZBTB14 downregulated TMEM208 expression through transcriptional repression. Overexpression of ZBTB14 significantly inhibited the malignant biological behavior of BC cells and tumor growth in vivo, and further upregulation of TMEM208 reversed the biological activity and radiotherapy resistance of RT-R/BC cells inhibited by overexpression of ZBTB14.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"20"},"PeriodicalIF":3.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"15th Annual ENBDC Meeting: How do Cellular Potency, Microenvironment and Natural Rhythms Influence Mammary Gland Biology and Breast Cancer?","authors":"Maria Rafaeva, Beata Kaczyńska, Jaime Redondo-Pedraza, Mohamed Bentires-Alj, Walid T Khaled, Silvia Fre","doi":"10.1007/s10911-024-09572-2","DOIUrl":"10.1007/s10911-024-09572-2","url":null,"abstract":"<p><p>Following previous editions, the fifteenth annual workshop of the European Network for Breast Development and Cancer (ENBDC) on Methods in Mammary Gland Biology and Breast Cancer was held from the 2nd to the 4th of May in Weggis, Switzerland. Over the course of this meeting, participants followed and discussed presentations from a roster of internationally renowned invited speakers and selected abstracts, complemented with two poster sessions covering exciting unpublished results. The sessions covered projects on normal mammary gland development, breast cancer evolution and metastasis, as well as epigenetic and metabolic regulation of breast cancer. As last year, early career researchers (ECR) hosted a pre-workshop day, when a stage was provided to allow PhD students and postdocs to showcase their projects and results, and when they had ample time for discussions on experimental settings and career planning, while interacting with several invited guests.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"19"},"PeriodicalIF":3.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational breast cancer: distinctive molecular and clinico-epidemiological features.","authors":"J R de la Haba-Rodríguez, P Mínguez, F Rojo, M Martín, E Alba, S Servitja, A Prat, J A Pérez-Fidalgo, J Gavilá, C Morales, A Rodriguez-Lescure, C Herrero, R Peña-Enriquez, J Herranz, C Hernando, A Hernández-Blanquisett, S Guil-Luna, M T Martinez, S Blanch, R Caballero, N Martín, M Pollán, A Guerrero-Zotano, B Bermejo","doi":"10.1007/s10911-024-09571-3","DOIUrl":"10.1007/s10911-024-09571-3","url":null,"abstract":"<p><p>Gestational breast cancer (GBC), defined as breast cancer (BC) diagnosed during pregnancy or the first-year post-partum, accounts for 6-15% of BC cases in women aged 20-44 years. GBC has worse prognosis than non-GBC, but reasons behind are not clear. The GEICAM/2012-03 Study (Molecular Characterization of Gestational Breast Cancer) is a multicenter prospective/retrospective observational registry of patients diagnosed with GBC. From November 2014 to June 2015 seventy patients diagnosed with GBC were included in the study, 30 diagnosed during pregnancy and 40 after delivery. Our current study was aimed to explore differences in epidemiological, clinico-pathological and gene expression features of GBC tumors, from the GEICAM/2012-03 Study, compared to non-GBC tumors from patients of similar age (< 43 years) from six different GEICAM studies, used as non- GBC control population. As per the main objective, the study found multiple differences showing GBC tumors as a different biological entity. GBC showed a more aggressive biology, with higher Ki67 levels, higher incidence of breast and/or ovarian cancer family history, and germline deleterious BRCA1/2 mutations, and are enriched in basal-like intrinsic subtype. GBC patients showed a lower number of tumor infiltrating lymphocytes, while specific genetic signatures highlight differences in GBC´s distinctive transcriptome. Our study shows that GBC is potentially a clinically and molecularly different entity, with specific epidemiological, clinical, and histological features, as well as a distinctive altered immune state and genetic signature. Nevertheless, further studies are needed to better understand the biology of GBC and to identify new targets against which develop new, more effective, targeted therapies.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"18"},"PeriodicalIF":3.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intramammary Labeling of Epithelial Cell Division.","authors":"Maia N Machiela, Russell C Hovey","doi":"10.1007/s10911-024-09570-4","DOIUrl":"10.1007/s10911-024-09570-4","url":null,"abstract":"<p><p>Thymidine analogs such as ethynyl deoxyuridine (EdU) or bromodeoxyuridine (BrdU) can be used to label mitosis of mammary epithelial cells (MEC) and to quantify their proliferation. However, labeling cells in larger animals requires considerable amounts of chemical that can be costly and hazardous. We developed a strategy to infuse EdU into the mammary glands of ewes to directly label mitotic MEC. First, each udder half of nulliparous ewes (n = 2) received an intramammary infusion of one of four different concentrations of EdU (0, 0.1, 1.0 or 10 mM) which was compared to BrdU IV (5 mg/kg) 24 h later. Tissues were analyzed by immunofluorescent histochemistry to detect EdU, BrdU, and total MEC. Of the EdU doses tested, 10 mM EdU yielded the greatest labeling index, while a proportion of MEC were labeled by both EdU and BrdU. We next sought to establish whether intramammary labeling could detect the induction of mitosis after exposure to exogenous estrogen and progesterone (E + P). We first infused EdU (10 mM) into the right udder half of ewes (n = 6) at t 0, followed by thymidine (100 mM) 24 h later to prevent further labeling. Three ewes were then administered E + P for 5 d, while n = 3 ewes served as controls. On d 5, EdU was infused into the left udder half of all mammary glands alongside BrdU IV (5 mg/kg). By the time of necropsy 24 h later an average MEC labeling index of 2.9% resulted from EdU delivered at t 0. In the left half of the udder on d 5, CON glands had a final EdU labeling index of 3.4% while glands exposed to E + P had a labeling index of 4.6% (p = 0.05). The corresponding degree of labeling with BrdU was 5.6% in CON glands, and 12% following E + P (p < 0.001). Our findings reveal that intramammary labeling is an efficient and cost-effective method for single- and dual-labeling of cell division in the mammary glands.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"17"},"PeriodicalIF":3.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Cell Contribution to Mammary Gland Development.","authors":"Ramiah Vickers, Weston Porter","doi":"10.1007/s10911-024-09568-y","DOIUrl":"10.1007/s10911-024-09568-y","url":null,"abstract":"<p><p>Postpartum breast cancer (PPBC) is a unique subset of breast cancer, accounting for nearly half of the women diagnosed during their postpartum years. Mammary gland involution is widely regarded as being a key orchestrator in the initiation and progression of PPBC due to its unique wound-healing inflammatory signature. Here, we provide dialogue suggestive that lactation may also facilitate neoplastic development as a result of sterile inflammation. Immune cells are involved in all stages of postnatal mammary development. It has been proposed that the functions of these immune cells are partially directed by mammary epithelial cells (MECs) and the cytokines they produce. This suggests that a more niche area of exploration aimed at assessing activation of innate immune pathways within MECs could provide insight into immune cell contributions to the developing mammary gland. Immune cell contribution to pubertal development and mammary gland involution has been extensively studied; however, investigations into pregnancy and lactation remain limited. During pregnancy, the mammary gland undergoes dramatic expansion to prepare for lactation. As a result, MECs are susceptible to replicative stress. During lactation, mitochondria are pushed to capacity to fulfill the high energetic demands of producing milk. This replicative and metabolic stress, if unresolved, can elicit activation of innate immune pathways within differentiating MECs. In this review, we broadly discuss postnatal mammary development and current knowledge of immune cell contribution to each developmental stage, while also emphasizing a more unique area of study that will be beneficial in the discovery of novel therapeutic biomarkers of PPBC.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"16"},"PeriodicalIF":3.1,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perimenopausal and Menopausal Mammary Glands In A 4-Vinylcyclohexene Diepoxide Mouse Model.","authors":"Kohei Saeki, Desiree Ha, Gregory Chang, Hitomi Mori, Ryohei Yoshitake, Xiwei Wu, Jinhui Wang, Yuan-Zhong Wang, Xiaoqiang Wang, Tony Tzeng, Hyun Jeong Shim, Susan L Neuhausen, Shiuan Chen","doi":"10.1007/s10911-024-09569-x","DOIUrl":"10.1007/s10911-024-09569-x","url":null,"abstract":"<p><p>As both perimenopausal and menopausal periods are recognized critical windows of susceptibility for breast carcinogenesis, development of a physiologically relevant model has been warranted. The traditional ovariectomy model causes instant removal of the entire hormonal repertoire produced by the ovary, which does not accurately approximate human natural menopause with gradual transition. Here, we characterized the mammary glands of 4-vinylcyclohexene diepoxide (VCD)-treated animals at different time points, revealing that the model can provide the mammary glands with both perimenopausal and menopausal states. The perimenopausal gland showed moderate regression in ductal structure with no responsiveness to external hormones, while the menopausal gland showed severe regression with hypersensitivity to hormones. Leveraging the findings on the VCD model, effects of a major endocrine disruptor (polybrominated diphenyl ethers, PBDEs) on the mammary gland were examined during and after menopausal transition, with the two exposure modes; low-dose, chronic (environmental) and high-dose, subacute (experimental). All conditions of PBDE exposure did not augment or compromise the macroscopic ductal reorganization resulting from menopausal transition and/or hormonal treatments. Single-cell RNA sequencing revealed that the experimental PBDE exposure during the post-menopausal period caused specific transcriptomic changes in the non-epithelial compartment such as Errfi1 upregulation in fibroblasts. The environmental PBDE exposure resulted in similar transcriptomic changes to a lesser extent. In summary, the VCD mouse model provides both perimenopausal and menopausal windows of susceptibility for the breast cancer research community. PBDEs, including all tested models, may affect the post-menopausal gland including impacts on the non-epithelial compartments.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"15"},"PeriodicalIF":3.1,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11254995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"State of the Art Modelling of the Breast Cancer Metastatic Microenvironment: Where Are We?","authors":"Mia Nuckhir, David Withey, Sara Cabral, Hannah Harrison, Robert B Clarke","doi":"10.1007/s10911-024-09567-z","DOIUrl":"10.1007/s10911-024-09567-z","url":null,"abstract":"<p><p>Metastatic spread of tumour cells to tissues and organs around the body is the most frequent cause of death from breast cancer. This has been modelled mainly using mouse models such as syngeneic mammary cancer or human in mouse xenograft models. These have limitations for modelling human disease progression and cannot easily be used for investigation of drug resistance and novel therapy screening. To complement these approaches, advances are being made in ex vivo and 3D in vitro models, which are becoming progressively better at reliably replicating the tumour microenvironment and will in the future facilitate drug development and screening. These approaches include microfluidics, organ-on-a-chip and use of advanced biomaterials. The relevant tissues to be modelled include those that are frequent and clinically important sites of metastasis such as bone, lung, brain, liver for invasive ductal carcinomas and a distinct set of common metastatic sites for lobular breast cancer. These sites all have challenges to model due to their unique cellular compositions, structure and complexity. The models, particularly in vivo, provide key information on the intricate interactions between cancer cells and the native tissue, and will guide us in producing specific therapies that are helpful in different context of metastasis.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"14"},"PeriodicalIF":3.1,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic Analysis of Pubertal and Adult Virgin Mouse Mammary Epithelial and Stromal Cell Populations.","authors":"Nika Heijmans, Katrin E Wiese, Jos Jonkers, Renée van Amerongen","doi":"10.1007/s10911-024-09565-1","DOIUrl":"10.1007/s10911-024-09565-1","url":null,"abstract":"<p><p>Conflicting data exist as to how mammary epithelial cell proliferation changes during the reproductive cycle. To study the effect of endogenous hormone fluctuations on gene expression in the mouse mammary gland, we performed bulk RNAseq analyses of epithelial and stromal cell populations that were isolated either during puberty or at different stages of the adult virgin estrous cycle. Our data confirm prior findings that proliferative changes do not occur in every mouse in every cycle. We also show that during the estrous cycle the main gene expression changes occur in adipocytes and fibroblasts. Finally, we present a comprehensive overview of the Wnt gene expression landscape in different mammary gland cell types in pubertal and adult mice. This work contributes to understanding the effects of physiological hormone fluctuations and locally produced signaling molecules on gene expression changes in the mammary gland during the reproductive cycle and should be a useful resource for future studies investigating gene expression patterns in different cell types across different developmental timepoints.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"13"},"PeriodicalIF":3.1,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rat Models of Hormone Receptor-Positive Breast Cancer.","authors":"Raquel Nicotra, Catrin Lutz, Hendrik A Messal, Jos Jonkers","doi":"10.1007/s10911-024-09566-0","DOIUrl":"10.1007/s10911-024-09566-0","url":null,"abstract":"<p><p>Hormone receptor-positive (HR⁺) breast cancer (BC) is the most common type of breast cancer among women worldwide, accounting for 70-80% of all invasive cases. Patients with HR⁺ BC are commonly treated with endocrine therapy, but intrinsic or acquired resistance is a frequent problem, making HR⁺ BC a focal point of intense research. Despite this, the malignancy still lacks adequate in vitro and in vivo models for the study of its initiation and progression as well as response and resistance to endocrine therapy. No mouse models that fully mimic the human disease are available, however rat mammary tumor models pose a promising alternative to overcome this limitation. Compared to mice, rats are more similar to humans in terms of mammary gland architecture, ductal origin of neoplastic lesions and hormone dependency status. Moreover, rats can develop spontaneous or induced mammary tumors that resemble human HR⁺ BC. To date, six different types of rat models of HR⁺ BC have been established. These include the spontaneous, carcinogen-induced, transplantation, hormone-induced, radiation-induced and genetically engineered rat mammary tumor models. Each model has distinct advantages, disadvantages and utility for studying HR⁺ BC. This review provides a comprehensive overview of all published models to date.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"12"},"PeriodicalIF":3.1,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methods for investigating STAT3 regulation of lysosomal function in mammary epithelial cells.","authors":"Bethan Lloyd-Lewis, Michael E D'Angelo, Neve B Prowting, Bethan E Wiseman, Timothy J Sargeant, Christine J Watson","doi":"10.1007/s10911-024-09563-3","DOIUrl":"10.1007/s10911-024-09563-3","url":null,"abstract":"<p><p>The transcription factor STAT3 is activated by multiple cytokines and other extrinsic factors. It plays a key role in immune and inflammatory responses and, when dysregulated, in tumourigenesis. STAT3 is also an indispensable mediator of the cell death process that occurs during post-lactational regression of the mammary gland, one of the most dramatic examples of physiological cell death in adult mammals. During this involution of the gland, STAT3 powerfully enhances the lysosomal system to efficiently remove superfluous milk-producing mammary epithelial cells via a lysosomal-mediated programmed cell death pathway. The lysosome is a membrane-enclosed  cytoplasmic organelle that digests and recycles cellular waste, with an important role as a signalling centre that monitors cellular metabolism. Here, we describe key strategies for investigating the role of STAT3 in regulating lysosomal function using a mammary epithelial cell culture model system. These include protocols for lysosome enrichment and enzyme activity assays, in addition to microscopic analyses of the vesicular compartment in cell lines. Collectively, these approaches provide the tools to investigate multiple aspects of lysosome biogenesis and function, and to define both direct and indirect roles for STAT3.</p>","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"29 1","pages":"11"},"PeriodicalIF":3.1,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11102350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}