The distribution of MUC1, an apical membrane glycoprotein, in mammary epithelial cells at the resolution of the electron microscope: implications for the mechanism of milk secretion

Mather, Ian H.; Jack, L. J. W.; Madara, Patricia; Johnson, Victoria

doi:10.1007/s004410100351

Cited by 35 publications

(27 citation statements)

References 73 publications

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“…Studies have shown that epithelial Muc1/MUC1 facilitates mucosal wound healing by enhancing cell migration and proliferation, protecting against apoptosis and mediating expression of mucosal modulators (35). In most epithelial-derived cancer cells, MUC1 is overexpressed and loses its apical polarity (36,37). In various adenocarcinoma including ESCC, MUC1 overexpression is correlated with tumor growth, lymph node metastasis and resistance to apoptosis (38), involved in multiple cancer-associated pathways.…”

Section: Discussionmentioning

confidence: 99%

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma

et al. 2015

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Abstract. MicroRNAs (miRNAs) are well known as important regulators in various cancer development. In the present study, we focused on the expression and biological function of miR-1291 in esophageal squamous cell carcinoma (ESCC). Compared with adjacent non-tumorous tissue samples, qRT-PCR data showed significant downregulation of miR-1291 in 54 ESCC tissue samples (P<0.05), which was also significantly associated with lymph node metastases and clinical stage (P<0.05). Cell Counting Kit-8 (CCK-8), colony formation, Transwell and flow cytometric apoptosis assays were performed to detect the effect of miR-1291 upregulation, and the results showed inhibition of the proliferation, invasion and promotion of apoptosis in EC9706 and EC-1 cells. Using bioinformatic analyses, we found that mucin 1 (MUC1) was a potential target for miR-1291. Luciferase assays were performed to reveal that miR-1291 inhibited MUC1 expression by targeting the seed region of MUC1 3'-untranslated region (3'UTR). We also found that the expression of MUC1 lacking in 3'UTR abrogated the anti-invasion and pro-apoptosis function of miR-1291. Our results demonstrated the importance of miR-1291 in targeting MUC1 for the regulation of esophagus cancer growth, invasion and apoptosis, and may be helpful for developing new targets for early diagnosis or new therapeutic targets for ESCC.

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Section: Discussionmentioning

confidence: 99%

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma

et al. 2015

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“…CD86 was also identified on the surface of vesicles derived from both the colostrum and mature milk of four of eight individuals at moderate levels. MUC-1, a glycoprotein that is present in large amounts in MFG (22), was detected in these vesicle fractions (Fig. 2B).…”

Section: Phenotypic Analysis Of the Vesiclesmentioning

confidence: 98%

Exosomes with Immune Modulatory Features Are Present in Human Breast Milk

Admyre

Johansson

Qazi

et al. 2007

The Journal of Immunology

1,056

867

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Breast milk is a complex liquid with immune-competent cells and soluble proteins that provide immunity to the infant and affect the maturation of the infant’s immune system. Exosomes are nanovesicles (30–100 nm) with an endosome-derived limiting membrane secreted by a diverse range of cell types. Because exosomes carry immunorelevant structures, they are suggested to participate in directing the immune response. We hypothesized that human breast milk contain exosomes, which may be important for the development of the infant’s immune system. We isolated vesicles from the human colostrum and mature breast milk by ultracentrifugations and/or immuno-isolation on paramagnetic beads. We found that the vesicles displayed a typical exosome-like size and morphology as analyzed by electron microscopy. Furthermore, they floated at a density between 1.10 and 1.18 g/ml in a sucrose gradient, corresponding to the known density of exosomes. In addition, MHC classes I and II, CD63, CD81, and CD86 were detected on the vesicles by flow cytometry. Western blot and mass spectrometry further confirmed the presence of several exosome-associated molecules. Functional analysis revealed that the vesicle preparation inhibited anti-CD3-induced IL-2 and IFN-γ production from allogeneic and autologous PBMC. In addition, an increased number of Foxp3+CD4+CD25+ T regulatory cells were observed in PBMC incubated with milk vesicle preparations. We conclude that human breast milk contains exosomes with the capacity to influence immune responses.

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“…It has been reported that BTN and XOR are expressed in constant molar proportions in bovine MFGM and these proportions vary with breed and stage of lactation. Particularly, XOR as a homodimer may simultaneously bind two BTN molecules and therefore be responsible for the observed accumulation of BTN molecules on budding membrane areas (Mather et al 2001). A likely explanation for the up-regulation of XOR during lactation is the high cellular demand for this structural molecule, since it is continuously lost from the cell with each budding fat droplet.…”

Section: Discussionmentioning

confidence: 99%

The housekeeping gene xanthine oxidoreductase is necessary for milk fat droplet enveloping and secretion: gene sharing in the lactating mammary gland

Vorbach¹,

Scriven²,

Capecchi³

2002

Genes Dev.

200

173

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Xanthine oxidoreductase (XOR) is the rate-limiting enzyme in purine catabolism occurring in most cell types. However, this housekeeping gene is expressed at very high levels in a number of mammalian tissues including the lactating mammary epithelium, suggesting additional roles for XOR in these tissues. Mice with targeted disruption of XOR were generated to assess these potential additional roles. XOR−/− mice are runted and do not live beyond 6 wk of age. Strikingly, however, XOR+/− females, although of healthy appearance and normal fertility, are unable to maintain lactation and their pups die of starvation 2 wk postpartum. Histological and whole-mount analyses showed that in XOR+/− females the mammary epithelium collapses, resulting in premature involution of the mammary gland. Electron microscopy showed that XOR is specifically required for enveloping milk fat droplets with the apical plasma membrane prior to secretion from the lactating mammary gland. We present evidence that XOR may have primarily a structural role, as a membrane-associated protein, in milk fat droplet secretion and thus XOR provides another example of "gene sharing". About 5% of women experience primary lactation insufficiency. The above observations suggest that human females suffering from xanthinuria, a deficiency in XOR, are potential candidates for lactation problems.

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The distribution of MUC1, an apical membrane glycoprotein, in mammary epithelial cells at the resolution of the electron microscope: implications for the mechanism of milk secretion

Cited by 35 publications

References 73 publications

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma

Exosomes with Immune Modulatory Features Are Present in Human Breast Milk

The housekeeping gene xanthine oxidoreductase is necessary for milk fat droplet enveloping and secretion: gene sharing in the lactating mammary gland

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