scholarly journals Methionine Protects Mammary Cells against Oxidative Stress through Producing S-Adenosylmethionine to Maintain mTORC1 Signaling Activity

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Heju Zhong ◽  
Peiqiang Yuan ◽  
Yunxia Li ◽  
Dolores Batonon-Alavo ◽  
Caroline Deschamps ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Treatment Time ◽  
Mammary Epithelial Cells ◽  
Mammary Glands ◽  
Mammary Epithelial ◽  
Mammary Cells ◽  
Mtorc1 Signaling ◽  
Signaling Activity

The mechanistic target of rapamycin complex 1 (mTORC1) signaling plays pivotal roles in cell growth and diseases. However, it remains mechanistically unclear about how to maintain mTORC1 activity during mammary glands development. Here we showed that mammary glands suffered from aggravated oxidative stress as pregnancy advanced and was accompanied by an increase in H2O2 levels, while the consumption for methionine and S-adenosylmethionine (SAM) rather than S-adenosylhomocysteine (SAH) were promoted in vivo. Likewise, H2O2 promoted SAM synthesis and reduced SAM utilization for methylation depending on H2O2 levels and treatment time in vitro. H2O2 inhibited phosphorylation of S6 kinase Thr 389 (p-S6K1 (T389)), 4E-BP1 Thr 37/46 and ULK1 Ser 757, the downstream of mTORC1, in mammary epithelial cells. However, methionine and SAM were shown to activate mTORC1 under H2O2-exposed condition. Moreover, this effect was not disabled by SGI-1027 which inhibits SAM transmethylation. In conclusion, methionine appeared to protect mammary cells against oxidative stress through producing SAM to maintain mTORC1 signaling activity.

scholarly journals The Fibronectin-Binding Proteins of Staphylococcus aureus May Promote Mammary Gland Colonization in a Lactating Mouse Model of Mastitis

2003 ◽  
Vol 71 (4) ◽  
pp. 2292-2295 ◽  
Author(s):  
Eric Brouillette ◽  
Brian G. Talbot ◽  
François Malouin
Keyword(s):  
Staphylococcus Aureus ◽  
Mouse Model ◽  
Binding Proteins ◽  
Mammary Epithelial Cells ◽  
Mammary Glands ◽  
Mammary Epithelial ◽  
Bovine Mammary Epithelial Cells ◽  
Fibronectin Binding

ABSTRACT The fibronectin-binding proteins (FnBPs) of Staphylococcus aureus are believed to be implicated in the pathogen's adherence to and colonization of bovine mammary glands, thus leading to infectious mastitis. In vitro studies have shown that FnBPs help the adhesion of the pathogen to bovine mammary epithelial cells. However, the importance of FnBPs for the infection of mammary glands has never been directly established in vivo. In this study with a mouse model of mastitis, the presence of FnBPs on the surface of S. aureus increased the capacity of the bacterium to colonize mammary glands under suckling pressure compared to that of a mutant lacking FnBPs.

scholarly journals A Dual Role for Oncostatin M Signaling in the Differentiation and Death of Mammary Epithelial Cells in Vivo

2008 ◽  
Vol 22 (12) ◽  
pp. 2677-2688 ◽  
Author(s):  
Paul G. Tiffen ◽  
Nader Omidvar ◽  
Nuria Marquez-Almuina ◽  
Dawn Croston ◽  
Christine J. Watson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Oncostatin M ◽  
Specific Gene ◽  
Mammary Involution

Abstract Recent studies in breast cancer cell lines have shown that oncostatin M (OSM) not only inhibits proliferation but also promotes cell detachment and enhances cell motility. In this study, we have looked at the role of OSM signaling in nontransformed mouse mammary epithelial cells in vitro using the KIM-2 mammary epithelial cell line and in vivo using OSM receptor (OSMR)-deficient mice. OSM and its receptor were up-regulated approximately 2 d after the onset of postlactational mammary regression, in response to leukemia inhibitory factor (LIF)-induced signal transducer and activator of transcription-3 (STAT3). This resulted in sustained STAT3 activity, increased epithelial apoptosis, and enhanced clearance of epithelial structures during the remodeling phase of mammary involution. Concurrently, OSM signaling precipitated the dephosphorylation of STAT5 and repressed expression of the milk protein genes β-casein and whey acidic protein (WAP). Similarly, during pregnancy, OSM signaling suppressed β-casein and WAP gene expression. In vitro, OSM but not LIF persistently down-regulated phosphorylated (p)-STAT5, even in the continued presence of prolactin. OSM also promoted the expression of metalloproteinases MMP3, MMP12, and MMP14, which, in vitro, were responsible for OSM-specific apoptosis. Thus, the sequential activation of IL-6-related cytokines during mammary involution culminates in an OSM-dependent repression of epithelial-specific gene expression and the potentiation of epithelial cell extinction mediated, at least in part, by the reciprocal regulation of p-STAT5 and p-STAT3.

scholarly journals Fine-tuning of Epithelial EGFR signals Supports Coordinated Mammary Gland Development

2020 ◽  
Author(s):  
Alexandr Samocha ◽  
Hanna M. Doh ◽  
Vaishnavi Sitarama ◽  
Quy H. Nguyen ◽  
Oghenekevwe Gbenedio ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelium ◽  
Gene Signature ◽  
Mammary Epithelial ◽  
Fine Tuning ◽  
Basal Cells ◽  
Stem And Progenitor Cells

SummaryDuring puberty, robust morphogenesis occurs in the mammary gland; stem- and progenitor-cells develop into mature basal- and luminal-cells to form the ductal tree. The receptor signals that govern this process in mammary epithelial cells (MECs) are incompletely understood. The EGFR has been implicated and here we focused on EGFR’s downstream pathway component Rasgrp1. We find that Rasgrp1 dampens EGF-triggered signals in MECs. Biochemically and in vitro, Rasgrp1 perturbation results in increased EGFR-Ras-PI3K-AKT and mTORC1-S6 kinase signals, increased EGF-induced proliferation, and aberrant branching-capacity in 3D cultures. However, in vivo, Rasgrp1 perturbation results in delayed ductal tree maturation with shortened branches and reduced cellularity. Rasgrp1-deficient MEC organoids revealed lower frequencies of basal cells, the compartment that incorporates stem cells. Molecularly, EGF effectively counteracts Wnt signal-driven stem cell gene signature in organoids. Collectively, these studies demonstrate the need for fine-tuning of EGFR signals to properly instruct mammary epithelium during puberty.

Effects of dietary fat on the growth of normal, preneoplastic and neoplastic mammary epithelial cells in vivo and in vitro

1985 ◽  
Vol 75 (1) ◽  
pp. 269-278 ◽  
Author(s):  
C.A. Carrington ◽  
H.L. Hosick
Keyword(s):  
Mammary Epithelial Cells ◽  
Saturated Fat ◽  
Mammary Epithelium ◽  
Mammary Epithelial ◽  
Dietary Fats ◽  
Polyunsaturated Fat ◽  
Fat Pad ◽  
Mammary Fat Pad

In order to determine: (1) whether there is a growth-regulating interaction between the mammary fat pad and mammary epithelium; (2) whether this interaction could be modified by dietary fats; and (3) whether these effects could be demonstrated in vitro, the following experiments were performed. Virgin Balb/c mice had the left inguinal mammary fat pad cleared of epithelium and were then maintained on one of four fully defined diets. These diets contained the following proportions of fat by weight: 5% or 10% mixed fats; 20% saturated fat plus cholesterol; or 20% polyunsaturated fat. To test for effects in vivo, animals received subcutaneous injections into the cleared fat pad of tumorigenic mammary cells (WAZ-2T(+SA) or WAZ-2T(-SA)) or preneoplastic mammary cells (CL-S1). Dietary fat had little effect on the latent period of tumour formation, but a low-fat diet increased the invasive/metastatic potential of both tumorigenic cell lines. A high-saturated-fat diet inhibited the growth of normal and preneoplastic epithelium in vivo. To test for effects in vitro, CL-S1 cells were co-cultured with explants of cleared mammary fat pad embedded within collagen gels. CL-S1 cells co-cultured with adipose explants obtained from mice fed on a diet containing 20% polyunsaturated fat showed a threefold increase in incorporation of [3H]thymidine into trichloroacetic acid-precipitable material. These results imply that dietary fats may affect the growth of mammary epithelium in two ways: the inhibition of growth caused by the high-saturated-fat diet may be due to systemic effects as it was not apparent in vitro; the increase in growth seen in vitro and caused by a high-polyunsaturated-fat diet is due to a direct interaction between the mammary fat pad and mammary epithelial cells. This interaction may be masked by systemic effects in vivo.

scholarly journals Regulatory function of whey acidic protein in the proliferation of mouse mammary epithelial cells in vivo and in vitro

2004 ◽  
Vol 274 (1) ◽  
pp. 31-44 ◽  
Author(s):  
Naoko Nukumi ◽  
Kayoko Ikeda ◽  
Megumi Osawa ◽  
Tokuko Iwamori ◽  
Kunihiko Naito ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Whey Acidic Protein ◽  
Mammary Epithelial ◽  
Acidic Protein ◽  
Regulatory Function

Menthol from Mentha piperita Suppresses the Milk Production of Lactating Mammary Epithelial Cells In Vivo and In Vitro

2020 ◽  
Vol 64 (24) ◽  
pp. 2000853
Author(s):  
Norihiro Suzuki ◽  
Yusaku Tsugami ◽  
Haruka Wakasa ◽  
Takahiro Suzuki ◽  
Takanori Nishimura ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Milk Production ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Mentha Piperita

Autocrine prolactin as a promotor of mammary tumour growth

2005 ◽  
Vol 72 (S1) ◽  
pp. 58-65 ◽  
Author(s):  
Caroline Manhes ◽  
Vincent Goffin ◽  
Paul A Kelly ◽  
Philippe Touraine
Keyword(s):  
Mammary Gland ◽  
Mammary Epithelial Cells ◽  
Physiological Role ◽  
Normal Growth ◽  
Mammary Epithelial ◽  
Alveolar Cells ◽  
Mammary Gland Differentiation

Prolactin (PRL) plays a key role in normal growth, development and differentiation of the mammary gland. Indeed, strong evidence suggests that the development of alveolar cells requires not only oestradiol and progesterone, but also PRL. In vitro, PRL has mitogenic activity on normal mouse mammary epithelial cells (reviewed in Das & Vonderhaar, 1997). In vivo, PRL also seems to be involved in such proliferative activity, although it is more difficult to distinguish the role of PRL from the influence of the hormonal milieu (Das & Vonderhaar, 1997). This physiological role of PRL in lobular development of the mammary gland is supported by results obtained from mice deficient for PRL (Horseman et al. 1997) or for its receptor (PRLR) (Ormandy et al. 1997). Although the infertility of females homozygous for the deletion of the PRLR gene (PRLR−/−) can be partially reversed by restoring progesterone levels close to normal, their mammary gland fails to differentiate during pregnancy, leading to lactation failure (Binart et al. 2000). In addition, heterozygous mice (PRLR+/−), who have half normal receptor levels, show impaired mammary gland development and fail to lactate following their first pregnancy, clearly indicating that signals mediated by the PRL/PRLR interaction have to achieve a certain level to permit mammary gland differentiation and lactation (Kelly et al. 2002). Since the pioneering work of Topper (Topper, 1970), who observed that PRL was necessary to induce casein synthesis, our understanding of the mechanism of such induction has greatly expanded. PRL appears to be the primary hormone involved in this activity, although other hormones such as insulin and glucocorticoids are also required for lactation.

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