Anterior gradient protein 2 is a marker of tumor aggressiveness in breast cancer and favors chemotherapy‑induced senescence escape

Triple-negative breast cancer (TNBC) is a major concern among the different subtypes of breast cancer (BC) due to the lack of effective treatment. In a previous study by our group aimed at understanding the difference between TNBC and non-TNBC tumors, we identified the gene TBC1 domain family member 9 (TBC1D9), the expression of which was lower in TNBC as compared to non-TNBC tumors. In the present study, analysis of TBC1D9 expression in TNBC (n = 58) and non-TNBC (n = 25) patient tumor samples validated that TBC1D9 expression can differentiate TNBC (low) from non-TNBC (high) samples and that expression of TBC1D9 was inversely correlated with grade and proliferative index. Moreover, we found that downregulation of the TBC1D9 gene decreases the proliferation marginally in non-TNBC and was associated with increased migratory and tumorigenic potential in both TNBC and luminal BC cell lines. This increase was mediated by the upregulation of ARL8A, ARL8B, PLK1, HIF1α, STAT3, and SPP1 expression in TBC1D9 knockdown cells. Our results suggest that TBC1D9 expression might limit tumor aggressiveness and that it has a differential expression in TNBC vs. non-TNBC tumors.

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DNA Topoisomerase II-Alpha Immunoreactivity as a Marker of Tumor Aggressiveness in Invasive Breast Cancer

Pathobiology ◽

10.1159/000055914 ◽

2000 ◽

Vol 68 (3) ◽

pp. 137-143 ◽

Cited By ~ 45

Author(s):

Lydia Nakopoulou ◽

Andreas C. Lazaris ◽

Nikolaos Kavantzas ◽

Paraskevi Alexandrou ◽

Pauline Athanassiadou ◽

...

Keyword(s):

Breast Cancer ◽

Invasive Breast Cancer ◽

Topoisomerase Ii ◽

Dna Topoisomerase Ii ◽

Tumor Aggressiveness ◽

Topoisomerase Ii Alpha ◽

Dna Topoisomerase

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Aberrant p63 and WT-1 expression in myoepithelial cells of pregnancy-associated breast cancer: implications for tumor aggressiveness and invasiveness

International Journal of Biological Sciences ◽

10.7150/ijbs.5.82 ◽

2009 ◽

pp. 82-96 ◽

Cited By ~ 8

Author(s):

Zheli Xu ◽

Wan Wang ◽

Chu-Xia Deng ◽

Yan-gao Man

Keyword(s):

Breast Cancer ◽

Myoepithelial Cells ◽

Tumor Aggressiveness

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Cyclooxygenase-2 (COX2) and p53 protein expression are interdependent in breast cancer but not associated with clinico-pathological surrogate subtypes, tumor aggressiveness and patient survival.

Acta Histochemica ◽

10.1016/j.acthis.2015.12.009 ◽

2016 ◽

Vol 118 (2) ◽

pp. 176-182 ◽

Cited By ~ 4

Author(s):

Katia Piton Serra ◽

Raquel Mary Rodrigues Peres ◽

Luis Otávio Sarian ◽

José Vassallo ◽

Glauce Aparecida Pinto ◽

...

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Patient Survival ◽

P53 Protein ◽

Cyclooxygenase 2 ◽

Tumor Aggressiveness ◽

P53 Protein Expression

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Breast density in Brazilian women and its risk for breast cancer and tumor aggressiveness

The Breast Journal ◽

10.1111/tbj.14042 ◽

2020 ◽

Vol 26 (11) ◽

pp. 2314-2315

Author(s):

Marina Dessimoni ◽

Carla Pessoa ◽

Benedito Filho ◽

Heloisa Vespoli ◽

Eliana Nahas ◽

...

Keyword(s):

Breast Cancer ◽

Breast Density ◽

Tumor Aggressiveness

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Melatonin regulates tumor aggressiveness under acidosis condition in breast cancer cell lines

Oncology Letters ◽

10.3892/ol.2018.9758 ◽

2018 ◽

Cited By ~ 6

Author(s):

Nath�lia Sonehara ◽

J�ssica Lacerda ◽

Bruna Jardim‑Perassi ◽

Rubens de Paula ◽

Marina Moschetta‑Pinheiro ◽

...

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Tumor Aggressiveness

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Anti-MUC1 Antibody in Nipple Aspirate Fluids Correlates with Tumor Aggressiveness in Breast Cancer: A Feasibility Study

Disease Markers ◽

10.1155/2015/179689 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6

Author(s):

Ebru Menekse ◽

John McKolanis ◽

Olivera J. Finn ◽

Priscilla F. McAuliffe ◽

Ronald Johnson ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Recurrent Disease ◽

Tumor Characteristics ◽

Tumor Aggressiveness ◽

Significant Difference ◽

Repeat Domain ◽

Nipple Aspirate Fluids ◽

Antibody Levels ◽

Igg Level

Antibodies against MUC1 are found in circulation of breast cancer (BC) patients. We hypothesized that anti-MUC1 antibodies might be present in even a higher concentration in nipple aspirate fluid (NAF) and could be used to predict aggressiveness of BC. Serum and NAF samples were collected from high risk lesions, BC, and healthy contralateral breasts. ELISA was used to measure the amount of IgG, IgM, and IgA against a tumor-specific MUC1 peptide derived from the extracellular tandem repeat domain of MUC1. Tumor characteristics were recorded prospectively; 120 NAF samples were obtained from a total of 77 women in the study. There was no significant difference of anti-MUC1 antibody levels compared to BC with other lesions. Anti-MUC1 IgG level in NAF was higher in triple negative tumors (P=0.02); serum anti-MUC1 IgG levels were significantly higher in patients with ER (−) tumor and recurrent disease (P=0.01); NAF anti-MUC1 IgA levels were significantly higher in patients with LVI and Her2-neu (+) tumors (P<0.05). These results show that NAF could be a reliable biomarker to predict tumor aggressiveness in BC. A larger study will be needed to confirm these data and to investigate the potential of anti-MUC1 antibodies in NAF and serum to predict disease outcome.

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MMP1, MMP9, and COX2 Expressions in Promonocytes Are Induced by Breast Cancer Cells and Correlate with Collagen Degradation, Transformation-Like Morphological Changes in MCF-10A Acini, and Tumor Aggressiveness

BioMed Research International ◽

10.1155/2013/279505 ◽

2013 ◽

Vol 2013 ◽

pp. 1-15 ◽

Cited By ~ 15

Author(s):

G. K. Chimal-Ramírez ◽

N. A. Espinoza-Sánchez ◽

D. Utrera-Barillas ◽

L. Benítez-Bribiesca ◽

J. R. Velázquez ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Immune Cells ◽

Immune Cell ◽

Morphological Changes ◽

Tumor Stroma ◽

Collagen Degradation ◽

Tumor Aggressiveness ◽

Soluble Factors ◽

Immune Effector

Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and noninvasive breast cancer cell (BRC) lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteasesMMP1andMMP9and inflammatoryCOX2genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets.

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