Two Faces of TGF-Beta1 in Breast Cancer

Zarzyńska, Joanna

doi:10.1155/2014/141747

Cited by 189 publications

(159 citation statements)

References 137 publications

(363 reference statements)

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“…The TGF-β pathway has a dual role in both tumor suppression and tumor promotion (Sheen et al, 2013). Zarzynska reported that in the early stages of breast cancer, TGF-β inhibited epithelial cell cycle progression and promoted apoptosis to suppress tumorigenesis (Zarzynska, 2014). Therefore, we suggest that PR might suppress tumorigenesis in DMBA-induced breast tumor rats by increasing TGF-β expression.…”

Section: Journal Of Agricultural Sciencementioning

confidence: 81%

Suppressive Effects of Puerariae Radix on the Breast Tumor Incidence in Rats Treated with DMBA

Chen¹,

Wu²,

Tseng³

et al. 2017

JAS

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Puerariae Radix (PR) is the root of Pueraria lobata, an herb widely used in traditional Chinese medicine and as a food seasoning. Owing to its potential anti-oxidative ability, the effects of PR on the inhibition of breast tumors were investigated in this study using the 7,12-dimethylbenz[a]anthracene (DMBA)-treated rat model. Thirty-two female Sprague-Dawley rats were randomly assigned to one of four different treatment groups, with or without PR and/or DMBA administration. At the age of 177 days, all rats were sacrificed, the number and size of tumors were recorded, and blood and tissue samples were collected for assessment of hematological parameters, redox status, and tumorigenesis-related factors. We found that PR supplementation decreased tumor incidence and WBC count but increased the IgM levels, and significantly altered the redox status, elevated serum TGF-β levels, and reduced serum VEGF-C and ICAM-1 levels. The mechanism by which PR decreased the incidence of DMBA-induced rat breast tumors might include ameliorating immunity, enhancing the antioxidant status, increasing the hepatic excretion of carcinogenic metabolites of DMBA, and influencing the expression of tumorigenesis-related factors.

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Section: Journal Of Agricultural Sciencementioning

confidence: 81%

Suppressive Effects of Puerariae Radix on the Breast Tumor Incidence in Rats Treated with DMBA

Chen¹,

Wu²,

Tseng³

et al. 2017

JAS

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“…The disparate action on DNA synthesis and nestin expression suggested that upregulation of the intermediate filament protein was insufficient to promote entry into the cell cycle in response to TGF-␤ 1 . Thus one or more of the myriad signaling events recruited by TGF-␤ 1 may have suppressed a downstream target of nestin required for DNA synthesis (41). Nonetheless, the in vitro data suggest that nestin upregulation in the vasculature of suprarenal abdominal aorta-constricted rats may have occurred in part via ANG II acting directly and/or in a concerted fashion via the synthesis and release of EGF and TGF-␤ 1 .…”

Section: Discussionmentioning

confidence: 97%

Nestin upregulation characterizes vascular remodeling secondary to hypertension in the rat

Tardif

Hertig

Duquette

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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The present study tested the hypothesis that vessel remodeling secondary to hypertension was characterized by nestin upregulation in vascular smooth muscle cells. Two weeks after suprarenal abdominal aorta constriction of adult male Sprague-Dawley rats, elevated mean arterial pressure increased the media area and thickness of the carotid artery and aorta and concomitantly upregulated nestin protein levels. In the normal adult rat carotid artery, nestin immunoreactivity was observed in a subpopulation of vascular smooth muscle cells, and the density significantly increased following suprarenal abdominal aorta constriction. Filamentous nestin was detected in cultured rat carotid arteryand aorta-derived vascular smooth muscle cells and an analogous paradigm observed in human aorta-derived vascular smooth muscle cells. ANG II and EGF treatment of vascular smooth muscle cells stimulated DNA and protein synthesis and increased nestin protein levels. Lentiviral short-hairpin RNA-mediated nestin depletion of carotid artery-derived vascular smooth muscle cells inhibited peptide growth factor-stimulated DNA synthesis, whereas protein synthesis remained intact. These data have demonstrated that vessel remodeling secondary to hypertension was characterized in part by nestin upregulation in vascular smooth muscle cells. The selective role of nestin in peptide growth factor-stimulated DNA synthesis has revealed that the proliferative and hypertrophic responses of vascular smooth muscle cells were mediated by divergent signaling events. nestin; carotid artery; aorta; hypertension; vascular remodeling DURING THE DEVELOPMENT of the central nervous system (CNS), a population of neuroepithelial stem cells was initially identified via expression of the intermediate filament protein nestin (8,18). Nestin is a 240-kDa protein and a member of the class VI family of intermediate filament proteins, and, in contrast to other classes, it is unable to self-assemble and form homodimers because of a short NH 2 terminus (37, 39). Therefore, nestin will form heterodimers with other intermediate filament proteins, including vimentin and desmin (37). The promoter region upstream of exon 1 of the nestin gene does not contain any identifiable elements regulating expression. However, the nestin gene does contain regulatory elements in the various intron regions that drive expression in a cell-specific manner (37). In neural progenitor/stem cells, nestin expression is independently regulated by restricted enhancer elements identified in the second intron (43). In humans, a highly conserved region that directed expression was also identified in the second intron of the nestin gene (21). However, nestin expression driven by the second intron was not limited to CNSresident stem cells, since a transgenic mouse containing the 5.8-kb fragment of the promoter region and the 1.8-kb fragment of the second intron of the rat nestin gene linked to the reporter green fluorescent protein (GFP) identified progenitor/ stem cell populations in the skin, skeletal mus...

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“…TGFb that acts as a tumor suppressor at early stages of cancer has also been shown to promote malignant properties of tumors, including invasion and metastasis at the later stages. It is found enriched in breast cancer bone metastasis (11). p53, on the other hand, has been shown to repress EMT by transcriptional repression of SNAIL and noncoding regulation mediated by miRNAs (12).…”

Section: Introductionmentioning

confidence: 99%

Stress Chaperone Mortalin Contributes to Epithelial-to-Mesenchymal Transition and Cancer Metastasis

Kaul

Ryu

et al. 2016

Cancer Research

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Mortalin/mthsp70 (HSPA9) is a stress chaperone enriched in many cancers that has been implicated in carcinogenesis by promoting cell proliferation and survival. In this study, we examined the clinical relevance of mortalin upregulation in carcinogenesis. Consistent with high mortalin expression in various human tumors and cell lines, we found that mortalin overexpression increased the migration and invasiveness of breast cancer cells. Expression analyses revealed that proteins involved in focal adhesion, PI3K-Akt, and JAK-STAT signaling, all known to play key roles in cell migration and epithelial-tomesenchymal transition (EMT), were upregulated in mortalinexpressing cancer cells. We further determined that expression levels of the mesenchymal markers vimentin (VIM), fibronectin (FN1), b-catenin (CTNNB1), CK14 (KRT14), and hnRNP-K were also increased upon mortalin overexpression, whereas the epithelial markers E-cadherin (CDH1), CK8 (KRT8), and CK18 (KRT18) were downregulated. Furthermore, shRNAmediated and pharmacologic inhibition of mortalin suppressed the migration and invasive capacity of cancer cells and was associated with a diminished EMT gene signature. Taken together, these findings support a role for mortalin in the induction of EMT, prompting further investigation of its therapeutic value in metastatic disease models. Cancer Res; 76(9);

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Two Faces of TGF-Beta1 in Breast Cancer

Cited by 189 publications

References 137 publications

Suppressive Effects of Puerariae Radix on the Breast Tumor Incidence in Rats Treated with DMBA

Suppressive Effects of Puerariae Radix on the Breast Tumor Incidence in Rats Treated with DMBA

Nestin upregulation characterizes vascular remodeling secondary to hypertension in the rat

Stress Chaperone Mortalin Contributes to Epithelial-to-Mesenchymal Transition and Cancer Metastasis

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