Immunohistochemical Detection of Activating Transcription Factor 3, a Hub of the Cellular Adaptive–Response Network

Hai, Tsonwin; Jalgaonkar, Swati; Wolford, Christopher C.; Yin, Xin

doi:10.1016/b978-0-12-385114-7.00011-8

Cited by 13 publications

(10 citation statements)

References 33 publications

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“…All staining procedures were performed as described previously [21]. Briefly, MCF-7 cells were plated on slide chambers and fixed with 10% neutral buffered formalin (Sigma).…”

Section: Methodsmentioning

confidence: 99%

Novel estrogen target gene ZAS3 is overexpressed in systemic lupus erythematosus

Young

Friedman

Kaffenberger

et al. 2013

Molecular Immunology

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Systemic lupus erythematosus (SLE) is a prototypic, inflammatory autoimmune disease characterized by significant gender bias. Previous studies have established a role for hormones in SLE pathogenesis, including the sex hormone estrogen. Estrogen regulates gene expression by translocating estrogen receptors (ER) α and β into the nucleus where they induce transcription by binding to estrogen response elements (EREs) of target genes. The ZAS3 locus encodes a signaling and transcriptional molecule involved in regulating inflammatory responses. We show that ZAS3 is significantly up-regulated in SLE patients at both the protein and mRNA levels in peripheral blood mononuclear cells (PBMCs). Furthermore, estrogen stimulates the expression of ZAS3 in vitro in several leukocyte and breast cancer cell lines of both human and murine origin. In vivo estrogen treatment mediates induction of tissue specific ZAS3 expression in several lymphoid organs in mice. Estrogen stimulation also significantly up-regulates ZAS3 expression in primary PBMCs, while treatment with testosterone has no effect. Mechanistically, estrogen induces differential ERα binding to putative EREs within the ZAS3 gene and ERα knockdown with siRNA prevents estrogen induced ZAS3 up-regulation. In contrast, siRNA targeting IFNα has no effect. These data demonstrate that ZAS3 expression is directly regulated by estrogen and that ZAS3 is overexpressed in lupus. Since ZAS3 has been shown to regulate inflammatory pathways, its up-regulation by estrogen could play a critical role in female-biased autoimmune disorders.

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“…All staining procedures were performed as described previously [21]. Briefly, MCF-7 cells were plated on slide chambers and fixed with 10% neutral buffered formalin (Sigma).…”

Section: Methodsmentioning

confidence: 99%

Novel estrogen target gene ZAS3 is overexpressed in systemic lupus erythematosus

Young

Friedman

Kaffenberger

et al. 2013

Molecular Immunology

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show abstract

“…S10 A and B. Immunohistochemistry, Immunofluorescent Staining, and Imaging Analyses. Staining was performed on formalin-fixed paraffin-embedded tissue sections as described previously (36,73) using the antibodies listed in SI Appendix, Table S1. After immunohistochemistry, the slides were counterstained with hematoxylin and captured on a Nikon Diaphot 300 microscope (Nikon).…”

Section: Discussionmentioning

confidence: 99%

Stress-inducible gene Atf3 in the noncancer host cells contributes to chemotherapy-exacerbated breast cancer metastasis

Chang

Jalgaonkar

Middleton

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Chemotherapy is a double-edged sword. It is anticancer because of its cytotoxicity. Paradoxically, by increasing chemoresistance and cancer metastasis, it is also procancer. However, the underlying mechanisms for chemotherapy-induced procancer activities are not well understood. Here we describe the ability of paclitaxel (PTX), a frontline chemotherapeutic agent, to exacerbate metastasis in mouse models of breast cancer. We demonstrate that, despite the apparent benefit of reducing tumor size, PTX increased the circulating tumor cells in the blood and enhanced the metastatic burden at the lung. At the primary tumor, PTX increased the abundance of the tumor microenvironment of metastasis, a landmark microanatomical structure at the microvasculature where cancer cells enter the blood stream. At the metastatic lung, PTX improved the tissue microenvironment (the "soil") for cancer cells (the "seeds") to thrive; these changes include increased inflammatory monocytes and reduced cytotoxicity. Importantly, these changes in the primary tumor and the metastatic lung were all dependent on Atf3, a stress-inducible gene, in the noncancer host cells. Together, our data provide mechanistic insights into the procancer effect of chemotherapy, explaining its paradox in the context of the seed-and-soil theory. Analyses of public datasets suggest that our data may have relevance to human cancers. Thus, ATF3 in the host cells links a chemotherapeutic agenta stressor-to immune modulation and cancer metastasis. Dampening the effect of ATF3 may improve the efficacy of chemotherapy.chemotherapy | metastasis | stress response | immune modulation | ATF3 M odern chemotherapy can reduce tumors to an undetectable level; however, in many cases the tumors relapse, with recurrence in the original, regional, or distant sites (1-3). The mechanisms for relapse are multifaceted and complex, including intrinsic changes in cancer cells and changes in the noncancer cells in the host-the organism carrying the cancer (4-9). Although the traditional concept is that chemotherapeutic drugs provide selection pressure for drug-resistant cancer cells to thrive, recent studies showed that chemotherapeutic drugs actually induce procancer changes (reviewed in refs. 4-9 and in the references cited below). Thus, chemotherapy is a double-edged sword: It is anticancer because of its cytotoxicity on cancer cells but also can be procancer by inducing changes in cancer and/or host cells. For cancer cell-intrinsic changes, chemotherapeutic drugs have been shown to induce the migration/invasion of cancer cells (10) and to up-regulate the expression of some antiapoptotic genes (11). For noncancer cells, chemotherapy theoretically can affect all host cells, because it is administered systemically. Advances in this nascent field have benefited greatly from the extensive literature on cancerhost interaction in the recent decades (5-7, 12). Although endothelial cells have been shown to play a role in mediating the procancer effect of chemotherapy (13-15), various reports als...

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“…3) suggested the C-19 antibody is less antigen-specific than the H-90 antibody when used in immunohistochemistry. Hai et al also recently pointed out this problem with the C-19 antibody [11]. Although there are several antibodies against ATF3 available commercially, their varying performances may lead to contrasting pancreatic expression patterns of ATF3.…”

Section: Atf3 Expression Is Increased By Low Glucose and Decreased Bymentioning

confidence: 99%

ATF3 expression is induced by low glucose in pancreatic α and β cells and regulates glucagon but not insulin gene transcription

et al. 2014

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Immunohistochemical Detection of Activating Transcription Factor 3, a Hub of the Cellular Adaptive–Response Network

Cited by 13 publications

References 33 publications

Novel estrogen target gene ZAS3 is overexpressed in systemic lupus erythematosus

Novel estrogen target gene ZAS3 is overexpressed in systemic lupus erythematosus

Stress-inducible gene Atf3 in the noncancer host cells contributes to chemotherapy-exacerbated breast cancer metastasis

ATF3 expression is induced by low glucose in pancreatic α and β cells and regulates glucagon but not insulin gene transcription

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