Showing papers on "Basal-Like Breast Carcinoma published in 2014"

Manganese Superoxide Dismutase Is a Promising Target for Enhancing Chemosensitivity of Basal-like Breast Carcinoma

Abstract: Aims: Although earlier reports highlighted a tumor suppressor role for manganese superoxide dismutase (MnSOD), recent evidence indicates increased expression in a variety of human cancers including aggressive breast carcinoma. In the present article, we hypothesized that MnSOD expression is significantly amplified in the aggressive breast carcinoma basal subtype, and targeting MnSOD could be an attractive strategy for enhancing chemosensitivity of this highly aggressive breast cancer subtype. Results: Using MDA-MB-231 and BT549 as a model of basal breast cancer cell lines, we show that knockdown of MnSOD decreased the colony-forming ability and sensitized the cells to drug-induced cell death, while drug resistance was associated with increased MnSOD expression. In an attempt to develop a clinically relevant approach to down-regulate MnSOD expression in patients with basal breast carcinoma, we employed activation of the peroxisome proliferator-activated receptor gamma (PPARγ) to repress MnSOD expression; PPARγ activation significantly reduced MnSOD expression, increased chemosensitivity, and inhibited tumor growth. Moreover, as a proof of concept for the clinical use of PPARγ agonists to decrease MnSOD expression, biopsies derived from breast cancer patients who had received synthetic PPARγ ligands as anti-diabetic therapy had significantly reduced MnSOD expression. Finally, we provide evidence to implicate peroxynitrite as the mechanism involved in the increased sensitivity to chemotherapy induced by MnSOD repression. Innovation and Conclusion: These data provide evidence to link increased MnSOD expression with the aggressive basal breast cancer, and underscore the judicious use of PPARγ ligands for specifically down-regulating MnSOD to increase the chemosensitivity of this subtype of breast carcinoma. Antioxid. Redox Signal. 20, 2326–2346.

Overexpression of Raf-1 in basal-like carcinoma of the breast: correlation with clinicopathology and prognosis

Abstract: Aim of the study: Increased Raf-1 expression has been associated with an aggressive behaviour in some carcinomas such as pulmonary carcinoma and renal carcinoma. However, its role in breast cancer, especially in basal-like carcinoma of the breast (BLBC), has not been defined. Material and methods: The current study attempted to investigate the expression pattern of Raf-1 protein in BLBC, in relation to the biological behaviour and prognosis of the carcinoma. Expression of Raf-1 was detected by immunohistochemistry in carcinoma specimens from 74 cases of BLBC, and associations between their expression and the clinicopathological characteristics were statistically assessed. Results: The patients’ age, tumour size, BRCA1, and p53 protein expression was not significantly different between the Raf-1-positive and Raf-1-negative expression groups (p > 0.05). The proportion of histological grade 3 tumours was not significantly higher in the Raf-1 positive group than that of grade 2 tumours (p > 0.05). However, positive cytoplasmic Raf-1 expression was positively correlated to Ki-67 expression (p < 0.05). Also, increased Raf-1 protein was found to exert an unfavourable impact on patients’ axillary lymph node metastasis and overall survival (p < 0.05). Conclusions: The study implies that positive Raf-1 expression in BLBC is associated with a more aggressive phenotype and could be considered as a new prognostic biomarker for poor survival in BLBC patients.

The expression of Cyclin D1 and its correlation with estrogen receptor and progesterone receptor in different molecular subtypes of breast cancer

Abstract: Objective To observe the expression of Cyclin D1 in different molecular subtypes of breast cancer and its relationship with estrogen receptor (ER),progesterone receptor (PR).Methods Typing molecular subtypes in 66 cases of breast cancer by immunohistochemical method to detect the expression of ER,PR,human epidermalgrowth factor receptor-2 (Her-2),creatine kinase 5/6 (CK5/6)and epidermal growth factor receptor(EGFR).And detect the expression of Cyclin D1 in different molecular subtypes in 66 cases with breast cancer to analysis the relationship between it and the molecular subtypes and ER,PR.Results (1) Cyclin D1 in the luminal A,luminal B,naked expression,over expression of Her-2 and basal like breast carcinoma positive expression rate decreased,respectively 85.71％,83.33 ％,75.00％,66.67％,44.44％,the difference was statistically significant (P ＜ 0.05).(2) The positive expression of ER was positively correlated with Cyclin D1 positive expression (r =0.436,P ＜0.05) ; and the positive expression of PR had no significant correlation with Cyclin D1 positive expression (r =0.048,P ＜ 0.05).Conclusion Cyclin D1 can be used as predictors of cancer prognosis and endocrine treatment in breast cancer. Key words: Breast cancer; Molecular subtype; Cyclin D1; Estrogen receptor; Progesterone receptor