Proteinases, cell cycle regulation, and apoptosis during mammary gland involution (minireview)

Wiesen, Jane; Werb, Zena

doi:10.1002/1098-2795(200008)56:4<534::aid-mrd12>3.0.co;2-o

Cited by 22 publications

(15 citation statements)

References 51 publications

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“…In the mammary gland cessation of lactation induces the secretion of metalloproteases that destroy the basement membrane to which milk-producing mammary epithelial cells are attached. As a consequence such cells undergo apoptosis that leads to mammary gland regression (8,9).…”

supporting

confidence: 86%

Cell Detachment Triggers p38 Mitogen-activated Protein Kinase-dependent Overexpression of Fas Ligand

Rosen

Shi

Calabretta

et al. 2002

Journal of Biological Chemistry

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Many cell types undergo apoptosis when they are detached from the extracellular matrix (ECM). This phenomenon has been termed anoikis. Most epithelial cells, which are normally attached to a type of ECM called basement membrane, are particularly sensitive to anoikis. Conversely, carcinoma cells tend to be resistant to anoikis, and this resistance plays a critical role in tumor invasion and metastasis. We reported previously that detachment-induced down-regulation of the antiapoptotic molecule Bcl-X L makes a significant contribution to anoikis of intestinal epithelial cells. Here we demonstrate that exogenous Bcl-X L , no matter how highly expressed in these cells, can significantly attenuate anoikis but cannot completely prevent it, suggesting that at least another pro-apoptotic event is activated by the loss of cell-ECM contacts. Indeed, in this study we identified a novel mechanism of anoikis in intestinal epithelial cells that involves detachment-induced overexpression of Fas ligand. We also demonstrated that this elevation in Fas ligand expression requires a detachment-induced increase of p38 mitogen-activated protein kinase activity. We conclude that the activation of at least two different pro-apoptotic events is required for anoikis of intestinal epithelial cells.

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supporting

confidence: 86%

Cell Detachment Triggers p38 Mitogen-activated Protein Kinase-dependent Overexpression of Fas Ligand

Rosen

Shi

Calabretta

et al. 2002

Journal of Biological Chemistry

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“…There is increasing awareness that many cultured cells require contact with an appropriate ECM to survive, and apoptosis due to loss of appropriate adhesion is referred to as "anoikis" (21,22). As in the case of HSC apoptosis during resolution of liver fibrosis (14), ECM remodeling is associated with apoptosis in vivo (23,24). In one of the best studied examples, unscheduled apoptosis of mouse mammary gland epithelial cells with consequent glandular involution was induced during weaning by forced overexpression of MMP-3 in these cells, an effect that was reduced when cells were induced to overexpress TIMP-1 (25).…”

mentioning

confidence: 62%

Engagement of αvβ3 Integrin Regulates Proliferation and Apoptosis of Hepatic Stellate Cells

Zhou¹,

Murphy²,

Gehdu³

et al. 2004

Journal of Biological Chemistry

202

160

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Hepatic stellate cells are the major source of the extracellular matrix that accumulates in fibrotic liver. During progressive liver fibrosis, hepatic stellate cells proliferate, but during resolution of fibrosis there is extensive stellate cell apoptosis that coincides with degradation of the liver scar. We have examined the possibility that the fate of stellate cells is influenced by the extracellular matrix through the intermediary of ␣ v ␤ 3 integrin. ␣ v ␤ 3 integrin was expressed by activated, myofibroblastic rat and human stellate cells in culture. Antagonism of this integrin using neutralizing antibodies, echistatin, or small inhibitory RNA to silence ␣ v subunit expression inhibited stellate cell proliferation and their expression of proliferating cell nuclear antigen and activated forms of p44 and p42 MAPK. These ␣ v ␤ 3 antagonists also increased apoptosis of cultured stellate cells, and this was associated with an increase in the BAX/ BCL-2 protein ratio, induction of nuclear DNA fragmentation, and activation of intracellular caspase-3. Expression of tissue inhibitor of metalloproteinases-1 by activated stellate cells was reduced by the ␣ v ␤ 3 antagonists, while matrix metalloproteinase-9 synthesis was enhanced. Stellate cells incubated with active recombinant matrix metalloproteinase-9 showed enhanced apoptosis, while cells treated with a synthetic inhibitor of this protease showed increased survival. Our studies suggest that ␣ v ␤ 3 integrin regulates the fate of hepatic stellate cells. Degradation of ␣ v ␤ 3 ligands surrounding activated stellate cells during resolution of liver fibrosis might decrease ␣ v ␤ 3 integrin ligation, suppressing stellate cell proliferation and inducing a fibrolytic, matrix metalloproteinase-secreting phenotype that may prime stellate cells for apoptosis.

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“…Pathological triggers of cell death in a number of other tissues are also associated with cell cycle reentry (Buttyan et al 1988, Colombel et al 1992, Pandey & Wang 1995, Wiesen & Werb 2000, Ecarnot-Laubriet et al 2002. Because the fully developed CL is composed predominantly of differentiated, nonproliferating cells, it was of interest to determine whether the physiological process of luteal regression is associated with cell cycle reentry.…”

Section: Introductionmentioning

confidence: 99%

Role of the cell cycle in regression of the corpus luteum

2013

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The corpus luteum contains differentiated steroidogenic cells that have exited the cell cycle of proliferation. In some tissues, deletion of quiescent, differentiated cells by apoptosis in response to injury or pathology is preceded by reentry into the cell cycle. We tested whether luteal cells reenter the cell cycle during the physiological process of luteolysis. Ovaries were obtained after injection of cows with a luteolytic dose of prostaglandin F 2a (PGF). In luteal sections, cells co-staining for markers of cell proliferation (MKI67) and apoptosis (cPARP1) increased 24 h after PGF, indicating that cells that reenter the cell cycle undergo apoptosis. The percent of steroidogenic cells (CYP11A1-positive) co-staining for MKI67 increased after PGF, while co-staining of non-steroidogenic cells did not change. Dispersed luteal cells were stained with Nile Red to distinguish lipid-rich steroidogenic cells from nonsteroidogenic cells and co-stained for DNA. Flow cytometry showed that the percent of steroidogenic cells progressing through the cell cycle and undergoing apoptosis increased after PGF. Culturing luteal cells induced reentry of steroidogenic cells into the cell cycle, providing a model to test the influence of the cell cycle on susceptibility to apoptosis. Blocking cells early in the cell cycle using inhibitors reduced cell death in response to treatment with the apoptosis-inducing protein, Fas ligand (FASL). Progesterone treatment reduced progression through the cell cycle and decreased FASL-induced apoptosis. In summary, steroidogenic cells reenter the cell cycle upon induction of luteal regression. While quiescent cells are resistant to apoptosis, entry into the cell cycle promotes susceptibility to apoptosis.

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Proteinases, cell cycle regulation, and apoptosis during mammary gland involution (minireview)

Cited by 22 publications

References 51 publications

Cell Detachment Triggers p38 Mitogen-activated Protein Kinase-dependent Overexpression of Fas Ligand

Cell Detachment Triggers p38 Mitogen-activated Protein Kinase-dependent Overexpression of Fas Ligand

Engagement of αvβ3 Integrin Regulates Proliferation and Apoptosis of Hepatic Stellate Cells

Role of the cell cycle in regression of the corpus luteum

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