Journal of Mammary Gland Biology and Neoplasia最新文献

Natural and induced epithelial-mesenchymal transition results in epigenetic silencing of HER2 overexpression. 自然和诱导的上皮-间质转化可导致HER2过表达的表观遗传沉默。

IF 3.6 4区医学

Journal of Mammary Gland Biology and Neoplasia Pub Date : 2025-09-30 DOI: 10.1007/s10911-025-09588-2

Kiandra N Hawkins, Jordan Dillard, Yin Ye, Justin Wang, Robert M Hoffman, Krista Mcphail, Sanford H Barsky

{"title":"Natural and induced epithelial-mesenchymal transition results in epigenetic silencing of HER2 overexpression.","authors":"Kiandra N Hawkins, Jordan Dillard, Yin Ye, Justin Wang, Robert M Hoffman, Krista Mcphail, Sanford H Barsky","doi":"10.1007/s10911-025-09588-2","DOIUrl":"10.1007/s10911-025-09588-2","url":null,"abstract":"Epithelial-mesenchymal transition (EMT) is a well-known phenomenon that has been implicated in diverse biological processes ranging from embryonal development to cancer invasion and metastasis. In epithelial-derived cancers which both invade and metastasize as epithelial clumps or clusters, EMT would have to be followed by MET (mesenchymal-epithelial transition) since both the initial cancer and the metastasis appear epithelial in nature. There is a rare subset of breast carcinomas, however, that exhibit biphasic epithelial and mesenchymal differentiation, so-called metaplastic carcinomas. Our initial studies were designed to examine whether EMT was indeed occurring in this unique subset of metaplastic breast carcinomas. Based on both RT-PCR and immunocytochemical studies, EMT was naturally occurring. Once this was confirmed, we wanted to investigate the effects of EMT beyond the immediate gene expression pattern that traditionally defined it. Although approximately 90% of metaplastic breast carcinomas are triple negative, 5-10% amplify and overexpress HER2. We then conducted both observational studies in these biphasic HER2 overexpressing metaplastic breast carcinomas and experimental studies with a HER2 overexpressing cell line, the HTB20, where TGFβ1 induced EMT. In the observational studies, HER2 gene amplification was equally present in both the epithelial and mesenchymal phases but both HER2 mRNA and protein levels were essentially silenced in the areas having undergone EMT. Similarly in the experimental studies where TGFβ1 induced EMT, HER2 gene amplification persisted but HER2 mRNA and protein levels were similarly silenced. These studies provide direct evidence that both naturally occurring and induced EMT results in epigenetically silencing of HER2 overexpression.","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"30 1","pages":"15"},"PeriodicalIF":3.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199743","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}

引用次数: 0

MaGNet: A Network-Based Method for Quantitative Analysis of the Mammary Ductal Tree in Developing Female Mice. 磁铁：一种基于网络的方法定量分析发育中的雌性小鼠乳腺导管树。

IF 3.6 4区医学

Journal of Mammary Gland Biology and Neoplasia Pub Date : 2025-09-26 DOI: 10.1007/s10911-025-09589-1

Steven M Lewis, Lucia Tellez-Perez, Samantha Henry, Xingyu Zheng, Saket Navlakha, Camila O Dos Santos

{"title":"MaGNet: A Network-Based Method for Quantitative Analysis of the Mammary Ductal Tree in Developing Female Mice.","authors":"Steven M Lewis, Lucia Tellez-Perez, Samantha Henry, Xingyu Zheng, Saket Navlakha, Camila O Dos Santos","doi":"10.1007/s10911-025-09589-1","DOIUrl":"10.1007/s10911-025-09589-1","url":null,"abstract":"The mammary gland is a uniquely dynamic organ with a branching architecture that develops entirely after birth in response to hormonal cues. A common approach in mammary gland biology is the evaluation of branching morphogenesis to characterize the role of developmental, physiological and molecular perturbations on branching tissue invasion, growth, and maintenance. Yet, the field still lacks a fully open-sourced, quantitative framework to analyze whole-mount mammary tissue images, as a commonly utilized methodology. Here, we present MaGNet (Mammary Gland Network analysis tool), a method that leverages network theory to characterize key features of ductal branching during mammary gland development. Applying this pipeline to mammary gland images captured at three pubertal timepoints, we achieved reproducible quantification of ductal tree expansion across development. In addition, this network analysis pipeline captures ductal expansion induced by pregnancy hormones. By providing open-source tools to the research community, this method may increase reproducibility and broad applicability across diverse organ systems, model organisms, and developmental stages.","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"30 1","pages":"13"},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149386","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}

引用次数: 0

Does microtubule motor-mediated centrosomal dyshomeostasis confer chemoresistance in breast cancer? 微管运动介导的中心体失衡是否导致乳腺癌的化疗耐药？

IF 3.6 4区医学

Journal of Mammary Gland Biology and Neoplasia Pub Date : 2025-09-26 DOI: 10.1007/s10911-025-09585-5

J Priyanga, Gunjan Guha, Dipita Bhakta-Guha

{"title":"Does microtubule motor-mediated centrosomal dyshomeostasis confer chemoresistance in breast cancer?","authors":"J Priyanga, Gunjan Guha, Dipita Bhakta-Guha","doi":"10.1007/s10911-025-09585-5","DOIUrl":"10.1007/s10911-025-09585-5","url":null,"abstract":"Chemoresistance is a major challenge in effective chemotherapy for breast cancers. Unfortunately, the precise molecular mechanisms that confer resistance remain elusive so far. A remarkable feature in a multitude of breast cancers is the presence of clustered supernumerary centrosomes, which is a dysregulated condition that arises primarily through centrosome over-duplication. Normally, microtubule motor proteins (MiMos) maintain the integrity of centrosomes via regulating cohesion, separation and positioning of centrosomes. In the recent years, several MiMos have been reported to be differentially expressed in chemoresistant breast cancers. Such findings suggest a probable association of MiMos with chemoresistance. Here, we propose that MiMo-associated centrosomal dysregulation is involved in conferring chemoresistance in breast cancers. We corroborate the same with a systematic review of literature where we narrow down to sixteen MiMos (one dynein and fifteen kinesins). Our argument highlights a plausible decisive role of MiMo-mediated centrosomal anomalies in orchestrating chemoresistance in breast cancers.","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"30 1","pages":"14"},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149402","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}

引用次数: 0

Live-cell imaging of mammary organoids using light sheet microscopy. 乳腺类器官的活细胞成像。

IF 3.6 4区医学

Journal of Mammary Gland Biology and Neoplasia Pub Date : 2025-09-01 DOI: 10.1007/s10911-025-09587-3

Matea Brezak, Azqa Ajmal Khan, Martin Jechlinger, Zuzana Sumbalova Koledova

引用次数: 0

Reactivation of Multipotency in the Mammary Gland - a Ripple in the Pond and a Turn of the Tide. 乳腺多能性的重新激活-池塘中的涟漪和潮汐的转变。

IF 3 4区医学

Journal of Mammary Gland Biology and Neoplasia Pub Date : 2025-07-17 DOI: 10.1007/s10911-025-09586-4

C Hager, C Jehanno, M Bentires-Alj

{"title":"Reactivation of Multipotency in the Mammary Gland - a Ripple in the Pond and a Turn of the Tide.","authors":"C Hager, C Jehanno, M Bentires-Alj","doi":"10.1007/s10911-025-09586-4","DOIUrl":"10.1007/s10911-025-09586-4","url":null,"abstract":"Multipotency refers to the ability of a cell to differentiate into multiple, yet limited as opposed to pluripotency, number of cell types within a specific lineage or tissue. Studies using transgenic mouse models of the mammary gland have revealed a cellular hierarchy in which both luminal and basal lineages are replenished by unipotent progenitor cells. Hence, despite the existence of bipotent stem cells, normal mammary gland homeostasis is intimately linked with unipotency. However, recent literature revealed that under specific physiological or experimental conditions, lineage-restricted mammary cells can reacquire multipotency and undergo a lineage switch, challenging the traditional unidirectional model of cell differentiation. This reactivation of multipotency has been observed, for instance, in response to pregnancy, lineage ablation or oncogenic stimuli, indicating a certain level of plasticity that may have consequences in the context of tumorigenesis. Understanding the molecular mechanisms governing this phenomenon could provide valuable insights into mammary gland cellular hierarchy and breast cancer progression. Indeed, reactivation of multipotency is a result of developed cell plasticity, which can drive tumor heterogeneity, promote disease aggressiveness and hamper diagnosis. This review provides an overview of models that have inferred reactivation of multipotency, discusses the underlying molecular and cellular mechanisms and proposes future perspectives for research.","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"30 1","pages":"11"},"PeriodicalIF":3.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659447","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}

引用次数: 0

Intraductal Injection of Adenoviruses to Perform Lineage Tracing in the Mammary Gland. 乳腺导管内注射腺病毒进行谱系追踪。

IF 3.6 4区医学

Journal of Mammary Gland Biology and Neoplasia Pub Date : 2025-07-07 DOI: 10.1007/s10911-025-09584-6

Xueqing Chen, Sen Han, Dongyi Zhao, Zhe Li

{"title":"Intraductal Injection of Adenoviruses to Perform Lineage Tracing in the Mammary Gland.","authors":"Xueqing Chen, Sen Han, Dongyi Zhao, Zhe Li","doi":"10.1007/s10911-025-09584-6","DOIUrl":"10.1007/s10911-025-09584-6","url":null,"abstract":"Lineage tracing is a fundamental tool in developmental biology and cancer research, providing critical insights into cell fate decisions, tissue homeostasis and tumor initiation. The mammary gland is a highly dynamic organ with a complex cellular hierarchy, making it an ideal system for lineage-tracing studies. Classic approaches, such as tamoxifen-inducible CreER/loxP recombination, have significantly advanced our understanding of mammary epithelial cell (MEC) differentiation, homeostasis, and transformation. However, these methods have limitations, including potential effects of tamoxifen on estrogen signaling, low mammary gland specificity, and the requirement for transgenic model creation and mouse breeding. Adenovirus-Cre (Ad-Cre)-based lineage tracing has emerged as a powerful alternative, enabling rapid and organ-specific recombination. This review provides a comprehensive evaluation of the Ad-Cre approach in mammary gland biology, comparing its efficiency, specificity, and technical advantages over the CreER-based method. We discuss applications of Ad-Cre intraductal injection-based lineage tracing in mapping MEC fates, identifying the cellular origins of breast cancer, and modeling tumor progression. Additionally, we highlight its ability to induce genetic marking at a clonal level, facilitating precise investigations into MEC plasticity and tumor cell heterogeneity. Despite its advantages, Ad-Cre lineage tracing also presents challenges, such as low cell-targeting efficiency and potential effect on the mammary gland immune microenvironment. Future advancements, including the integration of CRISPR-based barcoding, may further enhance its utility for high-resolution fate mapping. By summarizing recent advancements and comparative analyses, this review underscores the significance of Ad-Cre lineage tracing as a versatile and powerful tool in mammary gland biology and breast cancer research.","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"30 1","pages":"10"},"PeriodicalIF":3.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575675","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}

引用次数: 0

biogrowleR: Enhancing Longitudinal Data Analysis. biogrowleR：加强纵向数据分析。

IF 3 4区医学

Journal of Mammary Gland Biology and Neoplasia Pub Date : 2025-06-03 DOI: 10.1007/s10911-025-09583-7

Carlos Ronchi, Giovanna Ambrosini, Flavia Hughes, Renée L Flaherty, Hazel M Quinn, Daria Matvienko, Andrea Agnoletto, Cathrin Brisken

引用次数: 0

Developmental Regulation of circRNAs in Normal and Diseased Mammary Gland: A Focus on circRNA-miRNA Networks. 正常和病变乳腺中circrna的发育调控：circRNA-miRNA网络的研究

IF 3 4区医学

Journal of Mammary Gland Biology and Neoplasia Pub Date : 2025-05-02 DOI: 10.1007/s10911-025-09580-w

Sarah Marei, Nour Maatouk, Mounir AbouHaidar, Rabih Talhouk

{"title":"Developmental Regulation of circRNAs in Normal and Diseased Mammary Gland: A Focus on circRNA-miRNA Networks.","authors":"Sarah Marei, Nour Maatouk, Mounir AbouHaidar, Rabih Talhouk","doi":"10.1007/s10911-025-09580-w","DOIUrl":"https://doi.org/10.1007/s10911-025-09580-w","url":null,"abstract":"Circular RNAs (circRNAs) have emerged as critical regulators in various biological processes including diseases. In the mammary gland (MG), which undergoes most of its development postnatally, circRNAs play pivotal roles in both physiological and pathological contexts. This review highlights the involvement of circRNAs during key developmental stages of the MG, with particular emphasis on lactation, where circRNA-miRNA networks significantly influence milk secretion and composition. CircRNAs exhibit stage-, breed- and species-specific expression patterns during lactation, which underscores their complexity. This intricate regulation also plays a significant role in pathological conditions of the MG, where dysregulated circRNA expression contributes to disease progression such as mastitis, early breast cancer (BC) stages, and epithelial-to-mesenchymal transition in BC (EMT). In mastitis, altered circRNA expression disrupts immune responses and compromises epithelial integrity. During early BC progression, circRNAs drive cell proliferation, while in EMT, they facilitate metastatic processes. By focusing on the circRNA-miRNA interactions underlying these processes, this review highlights their potential use as biomarkers for MG development, disease progression, and as therapeutic targets.","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"30 1","pages":"8"},"PeriodicalIF":3.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011644","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}

引用次数: 0

Disease-Associated Mutations of the STAT5B SH2 Domain Regulate Cytokine-Driven Enhancer Function and Mammary Development. STAT5B SH2结构域的疾病相关突变调节细胞因子驱动的增强子功能和乳腺发育

IF 3 4区医学

Journal of Mammary Gland Biology and Neoplasia Pub Date : 2025-03-31 DOI: 10.1007/s10911-025-09582-8

Hye Kyung Lee, Jakub Jankowski, Chengyu Liu, Lothar Hennighausen

{"title":"Disease-Associated Mutations of the STAT5B SH2 Domain Regulate Cytokine-Driven Enhancer Function and Mammary Development.","authors":"Hye Kyung Lee, Jakub Jankowski, Chengyu Liu, Lothar Hennighausen","doi":"10.1007/s10911-025-09582-8","DOIUrl":"10.1007/s10911-025-09582-8","url":null,"abstract":"Mammary gland development during pregnancy is controlled by lactogenic hormones via the JAK2-STAT5 pathway. Gene deletion studies in mice have revealed the crucial roles of both STAT5A and STAT5B in establishing the genetic programs necessary for the development of mammary epithelium and successful lactation. Several hundred single nucleotide polymorphisms (SNPs) have been identified in human STAT5B, although their pathophysiological significance remains largely unknown. The SH2 domain is vital for STAT5B activation, and this study focuses on the impact of two specific missense mutations identified in T cell leukemias, the substitution of tyrosine 665 with either phenylalanine (Y665F) or histidine (Y665H). By introducing these human mutations into the mouse genome, we uncovered distinct and opposite functions. Mice harboring the STAT5BY665H mutation failed to develop functional mammary tissue, resulting in lactation failure, while STAT5BY665F mice exhibited accelerated mammary development during pregnancy. Transcriptomic and epigenomic analyses identified STAT5BY665H as Loss-Of-Function (LOF) mutation, impairing enhancer establishment and alveolar differentiation, whereas STAT5BY665F acted as a Gain-Of-Function (GOF) mutation, elevating enhancer formation. Persistent hormonal stimulation through two pregnancies led to the establishment of enhancer structures, gene expression and successful lactation in STAT5BY665H mice. Lastly, we demonstrate that Olah, a gene known to drive life-threatening viral disease in humans, is regulated by STAT5B through a candidate four-partite super-enhancer. In conclusion, our findings underscore the role of human STAT5B variants in modulating mammary gland homeostasis and their critical impact on lactation.","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"30 1","pages":"7"},"PeriodicalIF":3.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11958444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753086","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}

引用次数: 0

Association of ESR1, HER1, and HER2 Polymorphisms with Breast Cancer Risk in the KP Population, A Case-Control Study. 在KP人群中，ESR1、HER1和HER2多态性与乳腺癌风险的关联：一项病例对照研究

IF 3 4区医学

Journal of Mammary Gland Biology and Neoplasia Pub Date : 2025-03-27 DOI: 10.1007/s10911-025-09581-9

Najeeb Ullah Khan, Hamza Khan, Abdullah R Alanzi, Tianhui Chen

{"title":"Association of ESR1, HER1, and HER2 Polymorphisms with Breast Cancer Risk in the KP Population, A Case-Control Study.","authors":"Najeeb Ullah Khan, Hamza Khan, Abdullah R Alanzi, Tianhui Chen","doi":"10.1007/s10911-025-09581-9","DOIUrl":"10.1007/s10911-025-09581-9","url":null,"abstract":"Breast cancer is a complex disease characterized by the uncontrolled growth of breast cells. Genetic variants in ESR1, HER1, and HER2 have been associated with breast cancer risk across different populations, with varying results. This study aimed to validate the association of ESR1 (rs2234693 and rs2046210), HER1 (rs11543848), and HER2 (rs1136201) variants with breast cancer risk in the KP population of Pakistan using a larger dataset. The study cohort included 528 patients with BC and 530 healthy controls. Blood samples were collected, and DNA was extracted using a non-enzymatic method. Genotyping was performed using the T-ARMS-PCR protocol. Our results for ESR1 (rs2234693) indicated a non-significant association between the mutant C allele (P = 0.102), TC (P = 0.1002), and CC genotype (P = 0.398) and breast cancer risk. In contrast, ESR1 and rs2046210 showed a significant association with the mutant A allele (P = 0.001), GA (P = 0.001), and AA genotype (P = 0.001), indicating an increased risk. HER1 and rs11543848 showed an increased risk of breast cancer, with the mutant allele A (P = 0.001), GA (P = 0.001), and AA genotype (P = 0.001). Similarly, alleles G (P = 0.004), AG (P = 0.001), and GG genotype (P = 0.003) of HER2 (rs1136201) were associated with higher breast cancer risk. Furthermore, ESR1 (rs2234693) was significantly associated with PR status, while both HER1 (rs11543848) and HER2 (rs1136201) were considerably associated with HER2 receptor status. In conclusion, this study explored the association of the selected variants of ESR1, HER1, and HER2 with breast cancer risk in the KP population using a larger data set, providing valuable insights into the genetic factors contributing to breast cancer risk and corresponding value added to breast cancer management.","PeriodicalId":16413,"journal":{"name":"Journal of Mammary Gland Biology and Neoplasia","volume":"30 1","pages":"6"},"PeriodicalIF":3.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719901","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}

引用次数: 0