Breast tumors in PyMT transgenic mice expressing mitochondrial catalase have decreased labeling for macrophages and endothelial cells

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

We show by immunohistochemical labeling that prominent cell types in the tumor microenvironment of PyMT transgenic mice are tumor-associated macrophages (TAMs) and endothelial cells, and that both populations are decreased in the presence of mitochondrial targeted catalase (mCAT). This observation suggests that mitochondrial ROS can drive tumor invasiveness in conjunction with the presence of TAMs and increased angiogenesis. Since primary PyMT tumor cells expressing mCAT undergo increased apoptosis, mitochondrial antioxidants might be attractive anti-tumor agents.

Related collections

Most cited references 4

Record: found
Abstract: found
Article: not found

Pancreatic beta-cell failure and diabetes in mice with a deletion mutation of the endoplasmic reticulum molecular chaperone gene P58IPK.

Marcus Korth, F. Morton, Michael Katze … (2005)

The endoplasmic reticulum (ER) transmits apoptotic signals in the pancreas during ER stress, implicating ER stress-mediated apoptosis in the development of diabetes. P58(IPK) (DNAJC3) is induced during ER stress and functions as a negative feedback component to inhibit eIF-2alpha signaling and attenuate the later phases of the ER stress response. To gain insight into a more comprehensive role of P58(IPK) function, we generated deletion mutant mice that showed a gradual onset of glucosuria and hyperglycemia associated with increasing apoptosis of pancreatic islet cells. Lack of P58(IPK) had no apparent effect on the functional integrity of viable beta-cells. A set of genes associated with apoptosis showed altered expression in pancreatic islets from P58(IPK)-null mice, further substantiating the apoptosis phenotype. The data provide in vivo evidence to support the concept that P58(IPK) functions as a signal for the downregulation of ER-associated proteins involved in the initial ER stress response, thus preventing excessive cell loss by degradation pathways. Insulin deficiency associated with the absence of P58(IPK) mimics beta-cell failure associated with type 1 and late-stage type 2 diabetes. P58(IPK) function and activity may therefore provide a novel area of investigation into ER-mediated mechanistic and therapeutic approaches for diabetes.

0 comments Cited 61 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Reduction of age-associated pathology in old mice by overexpression of catalase in mitochondria.

P S Rabinovitch, Piper M. Treuting, F. Morton … (2008)

We describe the effects of mitochondrially targeted catalase (MCAT) expression on end-of-life pathology in mice using detailed semiquantitative histopathological evaluation. We previously reported that the median and maximum life spans of MCAT mice were extended relative to those of wild-type littermates. We now report that MCAT expression is associated with reduced malignant nonhematopoietic tumor burden, reduced cardiac lesions, and a trend toward reduced systemic inflammation, with no effect on hematopoietic neoplasia or glomerulonephropathy. Combined disease burden and comorbidity are also reduced, and MCAT expression is not associated with any detrimental clinical effects. The results suggest that oxidative damage is involved in aging of C57BL/6J mice via modulation of a subset of age-associated lesions. Antioxidant interventions targeting mitochondria may therefore be a viable strategy for prevention or postponement of some age-associated diseases. The variability of the MCAT effect across tissues, however, illustrates the importance of developing semiquantitative histopathology for assessment of comorbidity in life-span studies.

0 comments Cited 42 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Mitochondrial targeted catalase suppresses invasive breast cancer in mice

Jorming Goh, Linda Enns, Soroosh Fatemie … (2011)

Background Treatment of invasive breast cancer has an alarmingly high rate of failure because effective targets have not been identified. One potential target is mitochondrial generated reactive oxygen species (ROS) because ROS production has been associated with changes in substrate metabolism and lower concentration of anti-oxidant enzymes in tumor and stromal cells and increased metastatic potential. Methods Transgenic mice expressing a human catalase gene (mCAT) were crossed with MMTV-PyMT transgenic mice that develop metastatic breast cancer. All mice (33 mCAT positive and 23 mCAT negative) were terminated at 110 days of age, when tumors were well advanced. Tumors were histologically assessed for invasiveness, proliferation and metastatic foci in the lungs. ROS levels and activation status of p38 MAPK were determined. Results PyMT mice expressing mCAT had a 12.5 per cent incidence of high histological grade primary tumor invasiveness compared to a 62.5 per cent incidence in PyMT mice without mCAT. The histological grade correlated with incidence of metastasis with 56 per cent of PyMT mice positive for mCAT showing evidence of pulmonary metastasis compared to 85.4 per cent of PyMT mice negative for mCAT with pulmonary metastasis (p ≤ 0.05). PyMT tumor cells expressing mCAT had lower ROS levels and were more resistant to hydrogen peroxide-induced oxidative stress than wild type tumor cells, suggesting that mCAT has the potential of quenching intracellular ROS and subsequent invasive behavior. The metastatic tumor burden in PyMT mice expressing mCAT was 0.1 mm2/cm2 of lung tissue compared with 1.3 mm2/cm2 of lung tissue in PyMT mice expressing the wild type allele (p ≤ 0.01), indicating that mCAT could play a role in mitigating metastatic tumor progression at a distant organ site. Expression of mCAT in the lungs increased resistance to hydrogen peroxide-induced oxidative stress that was associated with decreased activation of p38MAPK suggesting ROS signaling is dependent on p38MAPK for at least some of its downstream effects. Conclusion Targeting catalase within mitochondria of tumor cells and tumor stromal cells suppresses ROS-driven tumor progression and metastasis. Therefore, increasing the antioxidant capacity of the mitochondrial compartment could be a rational therapeutic approach for invasive breast cancer. Please see related commentary article: http://www.biomedcentral.com/1741-7015/9/62

0 comments Cited 40 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Pathobiol Aging Age Relat Dis

Journal ID (iso-abbrev): Pathobiol Aging Age Relat Dis

Journal ID (publisher-id): PBA

Title: Pathobiology of Aging & Age Related Diseases

Publisher: Co-Action Publishing

ISSN (Electronic): 2001-0001

Publication date (Electronic): 11 May 2012

Publication date Collection: 2012

Volume: 2

Electronic Location Identifier: 10.3402/pba.v2i0.17391

Affiliations

Department of Comparative Medicine, University of Washington, Seattle, WA, USA

Author notes

[* ] Warren Ladiges, Department of Comparative Medicine, University of Washington, Seattle, WA 98195, USA. Email: wladiges@ 123456u.washington.edu

Article

Publisher ID: PBA-2-17391

DOI: 10.3402/pba.v2i0.17391

PMC ID: 3417526

PubMed ID: 22953034

SO-VID: b35652b9-dcda-462c-bdd4-08ed8b710d5a

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 12 February 2012

Date revision received : 16 April 2012

Date accepted : 16 April 2012

Breast tumors in PyMT transgenic mice expressing mitochondrial catalase have decreased labeling for macrophages and endothelial cells

Read this article at

Abstract

Related collections

Gamma Delta T cells

Most cited references 4

Pancreatic beta-cell failure and diabetes in mice with a deletion mutation of the endoplasmic reticulum molecular chaperone gene P58IPK.

Reduction of age-associated pathology in old mice by overexpression of catalase in mitochondria.

Mitochondrial targeted catalase suppresses invasive breast cancer in mice

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 504

Cited by 1

Most referenced authors 112