scholarly journals Androgen Receptor Expression and Bicalutamide Antagonize Androgen Receptor Inhibit β-Catenin Transcription Complex in Estrogen Receptor-Negative Breast Cancer

2017 ◽  
Vol 43 (6) ◽  
pp. 2212-2225 ◽  
Author(s):  
Rui Huang ◽  
Jiguang Han ◽  
Xiaoshuan Liang ◽  
Shanshan Sun ◽  
Yongdong Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Receptor Expression ◽  
Breast Cancer Cell Lines ◽  
Ki 67 ◽  
Cancer Subtypes ◽  
Invasive Ductal Cancer ◽  
Mechanistic Basis

Background/Aims: Little is known about the potential mechanism of action for androgen receptor (AR) targeting treatment in estrogen receptor (ER)-negative breast cancer. This study aimed to evaluate AR status and its prognosis in four breast cancer subtypes. Bicalutamide has been identified as an AR antagonist and used for treating AR+/ER- breast cancer in a phase II trial. Our studies will clarify its mechanism in breast cancer treatment. Methods: A total of 510 consecutive cases of invasive ductal cancer (IDC) were evaluated in this study. The expression of AR was analyzed by immunohistochemistry and compared with patient survival, and its implications were evaluated in four subtypes of IDC. We examined bicalutamide as an AR antagonist to inhibit proliferation and increased apoptosis in AR+/ER- breast cancer cell lines. We explored the tumor suppressive functions of bicalutamide in vitro and vivo and its related mechanisms in AR+/ER- breast cancer. Results: AR expression was related to that of ER (P<0.001), PR (P<0.001), Her2 (P=0.017), Ki-67(P=0.020) and to four subtypes (P<0.001). AR retained independent prognostic signifcance (P=0.007, ER- cases; P=0.001, ER+ cases; P=0.001, total cases). We found that bicalutamide significantly decreased viability and increased apoptosis in vitro and vivo. The mechanistic analysis revealed that bicalutamide blocked androgen-stimulated oncogenic AR and Wnt/β-catenin signaling and inhibited the growth of AR+/ER- breast cancer. Conclusion: Our studies provide novel insights into bicalutamide as an antagonist of AR function in AR+/ER- breast cancer and reveal the mechanistic basis for targeting AR as a therapeutic opportunity for patients with AR+/ER- breast cancer.

Association between androgen receptor expression, Ki-67 and the 21-gene recurrence score in non-metastatic, lymph node-negative, estrogen receptor-positive and HER2-negative breast cancer

2015 ◽  
Vol 68 (10) ◽  
pp. 839-843 ◽  
Author(s):  
Francisco E Vera-Badillo ◽  
Martin C Chang ◽  
Gordana Kuruzar ◽  
Alberto Ocana ◽  
Arnoud J Templeton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Lymph Node ◽  
Androgen Receptor ◽  
Statistical Significance ◽  
Multivariable Analysis ◽  
Recurrence Score ◽  
Receptor Expression ◽  
Ki 67 ◽  
Node Negative

BackgroundThe mechanisms underlying the favourable prognosis of androgen receptor (AR) expression in breast cancer are unknown.MethodsThe associations between the 21-gene recurrence score (RS), AR, grade, mitotic score, Ki-67 and estrogen receptor (ER) and progesterone receptor (PgR) expression were explored in sequential women with lymph node-negative, ER-positive and HER2-negative breast cancer. Statistical significance of this exploratory study was defined as p<0.10.ResultsAnalysis comprised 70 women. Most tumours had high AR expression (97% had scores >3). Median RS was 15 (range 1–53). AR expression showed a minimally significant positive correlation with ER (R=0.37), but no correlation with Ki-67 (R=−0.18). In univariable analysis, AR (p=0.01), ER (p<0.001) and PgR (p<0.001) had significant negative associations with RS. Ki-67 (p=0.16), grade (p=0.40) and mitotic score (p=0.23) showed no association with RS. Multivariable analysis showed similar associations.ConclusionsAR is associated with lower RS, but not with Ki-67.

scholarly journals Notch3 inhibits cell proliferation and tumorigenesis and predicts better prognosis in breast cancer through transactivating PTEN

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Yong-Qu Zhang ◽  
Yuan-Ke Liang ◽  
Yang Wu ◽  
Min Chen ◽  
Wei-Ling Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Malignant Tumors ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Loss Of Function ◽  
Ki 67 ◽  
Cancer Subtypes

AbstractNotch receptors (Notch1–4) play critical roles in tumorigenesis and metastasis of malignant tumors, including breast cancer. Although abnormal Notch activation is related to various tumors, the importance of single receptors and their mechanism of activation in distinct breast cancer subtypes are still unclear. Previous studies by our group demonstrated that Notch3 may inhibit the emergence and progression of breast cancer. PTEN is a potent tumor suppressor, and its loss of function is sufficient to promote the occurrence and progression of tumors. Intriguingly, numerous studies have revealed that Notch1 is involved in the regulation of PTEN through its binding to CBF-1, a Notch transcription factor, and the PTEN promoter. In this study, we found that Notch3 and PTEN levels correlated with the luminal phenotype in breast cancer cell lines. Furthermore, we demonstrated that Notch3 transactivated PTEN by binding CSL-binding elements in the PTEN promoter and, at least in part, inhibiting the PTEN downstream AKT-mTOR pathway. Notably, Notch3 knockdown downregulated PTEN and promoted cell proliferation and tumorigenesis. In contrast, overexpression of the Notch3 intracellular domain upregulated PTEN and inhibited cell proliferation and tumorigenesis in vitro and in vivo. Moreover, inhibition or overexpression of PTEN partially reversed the promotion or inhibition of cell proliferation induced by Notch3 alterations. In general, Notch3 expression positively correlated with elevated expression of PTEN, ER, lower Ki-67 index, and incidence of involved node status and predicted better recurrence-free survival in breast cancer patients. Therefore, our findings demonstrate that Notch3 inhibits breast cancer proliferation and suppresses tumorigenesis by transactivating PTEN expression.

scholarly journals Ki-67 Expression is a Significant Prognostic Factor Only When Progesterone Receptor Expression is Low in Estrogen Receptor-Positive and HER2-Negative Early Breast Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Young-Joon Kang ◽  
Han-Byoel Lee ◽  
Yun Gyoung Kim ◽  
JaiHong Han ◽  
Yumi Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Prognostic Factor ◽  
Progesterone Receptor ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Receptor Expression ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
End Point

Objective. While the value of Ki-67 has been recognized in breast cancer, controversy also exists. The goal of this study is to show the prognostic value of Ki-67 according to progesterone receptor (PgR) expression in patients who have estrogen receptor- (ER-) positive, human epidermal growth factor receptor 2- (HER2-) negative early breast cancer. Methods. The records of nonmetastatic invasive breast cancer patients who underwent surgery at a single institution between 2009 and 2012 were reviewed. Primary end point was recurrence-free survival (RFS), and secondary end point was overall survival (OS). Ki-67 and PgR were assessed with immunohistochemistry for the tumor after surgery. Results. A total of 1848 patients were enrolled in this study. 223 (12%) patients had high (≥10%) Ki-67, and 1625 (88%) had low Ki-67 expression. Significantly worse RFS and OS were observed in the high vs. low Ki-67 expression only when the PgR was low (<20%) (p<0.001 and 0.005, respectively, for RFS and OS). There was no significant difference in RFS and OS according to Ki-67 when the PgR was high (p=0.120 and 0.076). RFS of four groups according to high/low Ki-67 and PgR expression was compared. The low PgR and high Ki-67 expression group showed worst outcome among them (p<0.001). In a multivariate analysis, high Ki-67 was an independent prognostic factor when the PgR was low (HR 3.05; 95% CI 1.50–6.19; p=0.002). Conclusions. Ki-67 had a value as a prognostic factor only under low PgR expression level in early breast cancer. PgR should be considered in evaluating the prognosis of breast cancer patients using Ki-67.

scholarly journals Verteporfin Inhibits Cell Proliferation and Induces Apoptosis in Different Subtypes of Breast Cancer Cell Lines Without Light Activation

2020 ◽  
Author(s):  
Changran Wei ◽  
Xiangqi Li
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Hippo Pathway ◽  
Breast Cancer Cell Lines ◽  
Hippo Signaling ◽  
Luminal A ◽  
Ki 67 ◽  
Her 2

Abstract Background Breast cancer (BC) can be separated into four molecular subclassifications including Lumina1 A, Lumina1 B, HER-2 overexpression and Basal-like subtype. These classifications are based on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) and cell proliferation antigen (Ki-67). The Hippo signaling pathway plays an indispensable role in BC. The YAP1 gene is a terminal effector of Hippo pathway, and hyperactivation of YAP mediates tumorigenesis. As an inhibitor of YAP, non-photoactivated verteporfin (VP) can inhibit YAP-mediated tumor proliferation and angiogenesis by eliminating its interaction with TEAD. This study set out to determine the effect and molecular mechanisms of VP-mediated inhibition of YAP in different subtypes of BC. Methods Luminal A, Luminal B and Basal-like BC cells were cultivated in vitro in order to study effect of VP on proliferation and apoptosis on these three molecular BC subtypes. Results Our experimental results show that VP inhibits cell proliferation, YAP-TEAD interaction and its downstream target expression. VP also induces tumor cell apoptosis, and promotes the cleavage of Caspase-9 and PARP in various molecular subtypes of BC cells. Conclusion These findings provide a basis for VP as a potential anti-tumor therapeutic for BC by targeting the Hippo pathway effector YAP.

Evaluation of androgen receptor expression in core needle biopsies and clinico-pathological factors in primary breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12023-e12023
Author(s):  
Nobuyuki Arima ◽  
Reiki Nishimura ◽  
Tomofumi Osako ◽  
Yasuhiro Okumura ◽  
Masahiro Nakano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Neoadjuvant Chemotherapy ◽  
Needle Biopsy ◽  
Comparison Group ◽  
Ki 67 ◽  
Core Needle ◽  
Cancer Subtypes ◽  
The Core ◽  
Positive Rate

e12023 Background: Immunohistochemistry (IHC) is used to determine breast cancer subtypes and to evaluate the ER, PgR, and HER2 expressions and the Ki-67 index value. The androgen receptor (AR) is frequently expressed in breast cancer but has not been standardized. IHC is recommended when using preoperative biopsy specimens to determine biomarker expressions. In this study, the differences in AR expression between core needle biopsy and matched surgical samples were investigated. The AR expression was evaluated as a predictor for neoadjuvant chemotherapy and grade of malignancy. Methods: Primary breast cancer patients (n = 363) who underwent surgery between March 2017 and December 2018 were divided into 3 groups; the core needle biopsy and matched surgical comparison group (n = 167), the neoadjuvant chemotherapy group (n = 54), and the without neoadjuvant chemotherapy group (n = 309). The AR expression was evaluated using IHC and the expression was divided into the negative, low ( < 10%) and high (≥10%) groups. Breast cancer subtypes were categorized using the IHC data derived from ER/PgR, HER2 and Ki-67 (cutoff 20%) values. Results: 1. There was no difference between the ER, PgR and HER2 expressions in the comparison group. AR was significantly lower in the surgical specimens. 2. The pCR rate was significantly higher in the ER and PgR negative cases. AR and the Ki-67 value did not correlate with pCR. 3. The AR positive rate was 61.2% in invasive carcinoma cases. Apocrine carcinoma showed a 100% positive rate. 4. AR expression significantly correlated with positive ER and PgR, a lower Ki-67 value, negative p53, and a lower nuclear grade. Luminal A type showed a higher AR rate (78.2%) than the TN and HER2 types. The AR rate was significantly lower (17.1%) in the TN type cases. Conclusions: discordance in the AR expression between the core needle biopsies and matched surgical specimens was found. AR expression using IHC should be evaluated in core needle biopsies.

scholarly journals Expression of Annexin A2 Promotes Cancer Progression in Estrogen Receptor Negative Breast Cancers

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1582 ◽  
Author(s):  
Amira F. Mahdi ◽  
Beatrice Malacrida ◽  
Joanne Nolan ◽  
Mary E. McCumiskey ◽  
Anne B. Merrigan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cell Lines ◽  
Cancer Progression ◽  
Annexin A2 ◽  
Breast Cancer Progression ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Cancer Subtypes ◽  
Estrogen Receptor Negative

When breast cancer progresses to a metastatic stage, survival rates decline rapidly and it is considered incurable. Thus, deciphering the critical mechanisms of metastasis is of vital importance to develop new treatment options. We hypothesize that studying the proteins that are newly synthesized during the metastatic processes of migration and invasion will greatly enhance our understanding of breast cancer progression. We conducted a mass spectrometry screen following bioorthogonal noncanonical amino acid tagging to elucidate changes in the nascent proteome that occur during epidermal growth factor stimulation in migrating and invading cells. Annexin A2 was identified in this screen and subsequent examination of breast cancer cell lines revealed that Annexin A2 is specifically upregulated in estrogen receptor negative (ER-) cell lines. Furthermore, siRNA knockdown showed that Annexin A2 expression promotes the proliferation, wound healing and directional migration of breast cancer cells. In patients, Annexin A2 expression is increased in ER- breast cancer subtypes. Additionally, high Annexin A2 expression confers a higher probability of distant metastasis specifically for ER- patients. This work establishes a pivotal role of Annexin A2 in breast cancer progression and identifies Annexin A2 as a potential therapeutic target for the more aggressive and harder to treat ER- subtype.

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