scholarly journals Palb2 synergizes with Trp53 to suppress mammary tumor formation in a model of inherited breast cancer

2013 ◽  
Vol 110 (21) ◽  
pp. 8632-8637 ◽  
Author(s):  
C. Bowman-Colin ◽  
B. Xia ◽  
S. Bunting ◽  
C. Klijn ◽  
R. Drost ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Tumor ◽  
Tumor Formation ◽  
Inherited Breast Cancer

scholarly journals Methyl-CpG binding domain protein 2 plays a causal role in breast cancer growth and metastasis

2020 ◽  
Author(s):  
Niaz Mahmood ◽  
Ani Arakelian ◽  
Moshe Szyf ◽  
Shafaat A. Rabbani
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Mammary Tumor ◽  
Tumor Burden ◽  
Tumor Formation ◽  
Binding Domain ◽  
Causal Role ◽  
Molecular Signaling ◽  
Primary Tumors ◽  
Domain Protein

AbstractMethyl-CpG-binding domain protein 2 (Mbd2), a reader of DNA-methylation, has been implicated in the progression of several types of malignancies, including breast cancer. To test whether Mbd2, which is overexpressed in human breast cancer samples and in MMTV-PyMT mammary pads, plays a causal role in mammary tumor growth and metastasis we depleted Mbd2 in transgenic MMTV-PyMT model of breast cancer by cross-breeding with Mbd2 knockout mice to generate heterozygous (PyMT;Mbd2+/-) and homozygous (PyMT;Mbd2-/-) animals. We found that Mbd2 depletion caused a gene dose-dependent delay in mammary tumor formation, reduced primary tumor burden, and lung metastasis at the experimental endpoint. In addition, animals from the PyMT;Mbd2-/- group survived significantly longer compared to the wildtype (PyMT;Mbd2+/+) and PyMT;Mbd2+/- arms. Transcriptomic and proteomic analyses of the primary tumors obtained from PyMT;Mbd2+/+ and PyMT;Mbd2+/- groups revealed that Mbd2 depletion alters several key determinants of the molecular signaling networks related to tumorigenesis and metastasis, which thereby demonstrate that Mbd2 is regulating transcriptional programs critical for breast cancer. To our knowledge, this is the first study demonstrating a causal role for a DNA-methylation reader in breast cancer. Results from this study will provide the rationale for further development of first-in-class targeted epigenetic therapies against Mbd2 to inhibit the progression of breast and other common cancers.

scholarly journals Sulforaphane Diminishes the Formation of Mammary Tumors in Rats Exposed to 17β-Estradiol

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2282
Author(s):  
Dushani L. Palliyaguru ◽  
Li Yang ◽  
Dionysios V. Chartoumpekis ◽  
Stacy G. Wendell ◽  
Marco Fazzari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Mammary Tumor ◽  
Acid Metabolism ◽  
Slow Release ◽  
Mammary Tumorigenesis ◽  
Mammary Glands ◽  
Tumor Formation ◽  
Serum Free Fatty Acids ◽  
17Β Estradiol

Elevated levels of estrogen are a risk factor for breast cancer. In addition to inducing DNA damage, estrogens can enhance cell proliferation as well as modulate fatty acid metabolism that collectively contributes to mammary tumorigenesis. Sulforaphane (SFN) is an isothiocyanate derived from broccoli that is currently under evaluation in multiple clinical trials for prevention of several diseases, including cancer. Previous studies showed that SFN suppressed DNA damage and lipogenesis pathways. Therefore, we hypothesized that administering SFN to animals that are co-exposed to 17β-estradiol (E2) would prevent mammary tumor formation. In our study, 4–6 week old female August Copenhagen Irish rats were implanted with slow-release E2 pellets (3 mg x 3 times) and gavaged 3x/week with either vehicle or 100 μmol/kg SFN for 56 weeks. SFN-treated rats were protected significantly against mammary tumor formation compared to vehicle controls. Mammary glands of SFN-treated rats showed decreased DNA damage while serum free fatty acids and triglyceride species were 1.5 to 2-fold lower in SFN-treated rats. Further characterization also showed that SFN diminished expression of enzymes involved in mammary gland lipogenesis. This study indicated that SFN protects against breast cancer development through multiple potential mechanisms in a clinically relevant hormonal carcinogenesis model.

scholarly journals Ron Receptor Signaling Augments Mammary Tumor Formation and Metastasis in a Murine Model of Breast Cancer

2005 ◽  
Vol 65 (4) ◽  
pp. 1285-1293 ◽  
Author(s):  
Belinda E. Peace ◽  
Kenya Toney-Earley ◽  
Margaret H. Collins ◽  
Susan E. Waltz
Keyword(s):  
Breast Cancer ◽  
Mammary Tumor ◽  
Murine Model ◽  
Tumor Formation ◽  
Receptor Signaling ◽  
Ron Receptor

Combination of Histone Deacetylase Inhibitor with Cu(II) 5,5- diethylbarbiturate Complex Induces Apoptosis in Breast Cancer Stem Cells: A Promising Novel Approach

2020 ◽  
Vol 21 ◽  
Author(s):  
Merve Erkisa ◽  
Nazlihan Aztopal ◽  
Elif Erturk ◽  
Engin Ulukaya ◽  
Veysel T. Yilmaz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Histone Deacetylases ◽  
Caspase 3 ◽  
Cancer Cell Line ◽  
Annexin V ◽  
Tumor Formation ◽  
Dependent Manner

Background: Cancer stem cells (CSC) are subpopulation within the tumor that acts a part in the initiation, progression, recurrence, resistance to drugs and metastasis of cancer. It is well known that epigenetic changes lead to tumor formation in cancer stem cells and show drug resistance. Epigenetic modulators and /or their combination with different agents have been used in cancer therapy. Objective: In our study we scope out the effects of combination of a histone deacetylases inhibitor, valproic acid (VPA), and Cu(II) complex [Cu(barb-κN)(barb-κ2N,O)(phen-κN,N’)]·H2O] on cytotoxicity/apoptosis in a stem-cell enriched population (MCF-7s) obtained from parental breast cancer cell line (MCF-7). Methods: Viability of the cells was measured by the ATP assay. Apoptosis was elucidated via the assessment of caspase-cleaved cytokeratin 18 (M30 ELISA) and a group of flow cytometry analysis (caspase 3/7 activity, phosphatidylserine translocation by annexin V-FITC assay, DNA damage and oxidative stress) and 2ˈ,7ˈ–dichlorofluorescein diacetate staining. Results: The VPA combined with Cu(II) complex showed anti proliferative activity on MCF-7s cells in a dose- and time-dependently. Treatment with combination of 2.5 mM VPA and 3.12 μM Cu(II) complex induces oxidative stress in a time-dependent manner, as well as apoptosis that is evidenced by the increase in caspase 3/7 activity, positive annexin-V-FITC, and increase in M30 levels. Conclusion: The results suggest that the combination therapy induces apoptosis following increased oxidative stress, thereby making it a possible promising therapeutic strategy that further analysis is required.

scholarly journals Comparison of SYK Signaling Networks Reveals the Potential Molecular Determinants of Its Tumor-Promoting and Suppressing Functions

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 308
Author(s):  
Marion Buffard ◽  
Aurélien Naldi ◽  
Gilles Freiss ◽  
Marcel Deckert ◽  
Ovidiu Radulescu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Signaling Pathways ◽  
Burkitt Lymphoma ◽  
Molecular Mechanisms ◽  
Signal Propagation ◽  
Tumor Formation ◽  
Tissue Type ◽  
Signaling Networks ◽  
Proteomic Profiling

Spleen tyrosine kinase (SYK) can behave as an oncogene or a tumor suppressor, depending on the cell and tissue type. As pharmacological SYK inhibitors are currently evaluated in clinical trials, it is important to gain more information on the molecular mechanisms underpinning these opposite roles. To this aim, we reconstructed and compared its signaling networks using phosphoproteomic data from breast cancer and Burkitt lymphoma cell lines where SYK behaves as a tumor suppressor and promoter. Bioinformatic analyses allowed for unveiling the main differences in signaling pathways, network topology and signal propagation from SYK to its potential effectors. In breast cancer cells, the SYK target-enriched signaling pathways included intercellular adhesion and Hippo signaling components that are often linked to tumor suppression. In Burkitt lymphoma cells, the SYK target-enriched signaling pathways included molecules that could play a role in SYK pro-oncogenic function in B-cell lymphomas. Several protein interactions were profoundly rewired in the breast cancer network compared with the Burkitt lymphoma network. These data demonstrate that proteomic profiling combined with mathematical network modeling allows untangling complex pathway interplays and revealing difficult to discern interactions among the SYK pathways that positively and negatively affect tumor formation and progression.

scholarly journals Obesity-Activated Lung Stromal Cells Promote Myeloid Lineage Cell Accumulation and Breast Cancer Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1005
Author(s):  
Lauren E. Hillers-Ziemer ◽  
Abbey E. Williams ◽  
Amanda Janquart ◽  
Caitlin Grogan ◽  
Victoria Thompson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stromal Cells ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Breast Cancer Metastasis ◽  
Tumor Formation ◽  
Obese Mouse ◽  
Obese Mice ◽  
Myeloid Lineage ◽  
Primary Tumors

Obesity is correlated with increased incidence of breast cancer metastasis; however, the mechanisms underlying how obesity promotes metastasis are unclear. In a diet-induced obese mouse model, obesity enhanced lung metastasis in both the presence and absence of primary mammary tumors and increased recruitment of myeloid lineage cells into the lungs. In the absence of tumors, obese mice demonstrated increased numbers of myeloid lineage cells and elevated collagen fibers within the lung stroma, reminiscent of premetastatic niches formed by primary tumors. Lung stromal cells isolated from obese tumor-naïve mice showed increased proliferation, contractility, and expression of extracellular matrix, inflammatory markers and transforming growth factor beta-1 (TGFβ1). Conditioned media from lung stromal cells from obese mice promoted myeloid lineage cell migration in vitro in response to colony-stimulating factor 2 (CSF2) expression and enhanced invasion of tumor cells. Together, these results suggest that prior to tumor formation, obesity alters the lung microenvironment, creating niches conducive to metastatic growth.

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