Sheng Gao

Perfluorooctanoic acid stimulates breast cancer cells invasion and up-regulates matrix metalloproteinase-2/-9 expression mediated by activating NF-κB.

Perfluorooctanoic acid (PFOA) is widely used because of its stain-resistant and water-repellant properties. This study aimed to explore the molecular mechanisms undergoing the stimulation effects of PFOA on cancer cell invasion and matrix metalloproteinases (MMPs) expression. Trans-well filter assay showed that PFOA exposure (≥5 nM) evidently enhanced the invasion ability of the breast cancer cells MDA-MB-231. Luciferase reporter assay, quantitative real-time PCR, western blotting and gelatin zymography consistently demonstrated that mRNA and protein levels of MMP-2/-9 were increased in the cells after PFOA treatment (P<0.05 each). Western blotting revealed that PFOA could activate nuclear factor kappaB (NF-κB) by accelerating NF-κB translocation into the nucleus. Furthermore, addition of NF-κB inhibitor in culture medium could suppress the breast cancer cells invasiveness enhancement and MMP-2/-9 overexpression. This study indicates that PFOA can stimulate breast cancer cells invasion and up-regulate matrix metalloproteinase-2/-9 expression mediated by activating NF-κB, which deserves more environmental health concerns.

Mammary Fat of Breast Cancer: Gene Expression Profiling and Functional Characterization

Mammary fat is the main composition of breast, and is the most probable candidate to affect tumor behavior because the fat produces hormones, growth factors and adipokines, a heterogeneous group of signaling molecules. Gene expression profiling and functional characterization of mammary fat in Chinese women has not been reported. Thus, we collected the mammary fat tissues adjacent to breast tumors from 60 subjects, among which 30 subjects had breast cancer and 30 had benign lesions. We isolated and cultured the stromal vascular cell fraction from mammary fat. The expression of genes related to adipose function (including adipogenesis and secretion) was detected at both the tissue and the cellular level. We also studied mammary fat browning. The results indicated that fat tissue close to malignant and benign lesions exhibited distinctive gene expression profiles and functional characteristics. Although the mammary fat of breast tumors atrophied, it secreted tumor growth stimulatory factors. Browning of mammary fat was observed and browning activity of fat close to malignant breast tumors was greater than that close to benign lesions. Understanding the diversity between these two fat depots may possibly help us improve our understanding of breast cancer pathogenesis and find the key to unlock new anticancer therapies.

Exposure to bisphosphonates and risk of colorectal cancer.

Animal and in vitro studies suggest that the use of bisphosphonates (BPs) may be associated with reduced risk for colorectal cancer (CRC). However, results from these studies have been inconsistent. The aim of our study was to review and summarize the evidence provided by longitudinal studies on the association between BP use and CRC risk A comprehensive literature search for articles published up to October 2012 was performed. Prior to performing a meta-analysis, the studies were evaluated for publication bias and heterogeneity. Relative risks (RRs) or odds ratios were calculated. Six reports (four case-control studies and two cohort studies) published between 2010 and 2012 were identified. There was evidence of an association between any use of BPs and CRC risk using a fixed-effects model (RR = 0.80, 95% confidence interval = 0.74, 0.85) and a random-effects model (RR = 0.80, 95% confidence interval = 0.71, 0.90). However, we did not observe any evidence of a trend with increasing duration of use. Our findings indicate that there is evidence of an association between any use of BP and reduced CRC risk. However, this subject deserves further investigation.

Long noncoding RNAs (lncRNAs) in triple negative breast cancer

Long noncoding RNAs (lncRNAs) are dysregulated in many cancer types, which are believed to play crucial roles in regulating several hallmarks of cancer biology. Triple Negative Breast Cancer (TNBC) is a very aggressive subtype of normal breast cancer, which has features of negativity for ER, PR, and HER2. Great efforts have been made to identify an association between lncRNAs expression profiles and TNBC, and to understand the functional role and molecular mechanism on aberrant‐expressed lncRNAs. In this review, we summarized the existed knowledge on the systematics, biology, and function of lncRNAs. The advances from the most recent studies of lncRNAs in the predicament of breast cancer, TNBC, are highlighted, especially the functions of specifically selected lncRNAs. We also discussed the potential value of these lncRNAs in TNBC, providing clues for the diagnosis and treatments of TNBC.

SPARC inhibits breast cancer bone metastasis and may be a clinical therapeutic target

Breast cancer is one of the most common types of cancer in females worldwide, and metastasis to bone is an important characteristic of malignancy. The present study aimed to investigate the molecular mechanism of breast cancer to bone metastasis of secreted protein acidic and rich in cysteine (SPARC). Immunohistochemistry was performed to examine the expression of SPARC in primary breast tumors and bone metastatic foci. Western blotting and reverse transcription-quantitative polymerase chain reaction were performed to detect the expression level of SPARC in several types of breast cancer cell. A Transwell filter assay was used to assess the effect of SPARC on breast cancer cell invasion ability, and an osteoblast differentiation assay was employed to analyze the effect of SPARC on the differentiation ability of mesenchymal stem cells. Clinical data revealed that decreased stromal SPARC expression is associated with breast cancer to bone metastasis. Gain- and loss-of-function studies reveal that SPARC inhibits the migration and invasion of breast cancer cells, and suppresses osteoclast activation in the breast cancer microenvironment. SPARC serves an important role in breast cancer bone metastasis and may be a promising therapeutic target for the treatment of breast cancer bone metastasis.

Comprehensive profiling of biological processes reveals two major prognostic subtypes in breast cancer.

Heterogeneity is the major obstacle to breast cancer target therapy. Classification of breast cancer with significant biological process may reduce the influence of heterogeneity of intrinsic tumor. We used survival analysis to filter 95 gene sets and classify 638 breast cancer samples into two subtypes based on those gene sets associated with prognosis. Clinical outcome of two subtypes were evaluated with disease-free survival, distant metastasis-free survival, and overall survival levels in three databases and ER+, PR+ HER2+, and TNBC groups. We established a novel classification with 95 prognostic gene sets. In the training and validation cohorts, the subtype 1 was characterized by significant gene sets associated with regulation of metabolic process and enzyme activity and predicted obviously improved clinical outcome than subtype 2, which was enriched by tumor cell division, mitosis, and cell cycle-related gene sets (P < 0.05). When evaluated prognostic impact of subtypes in ER+, PR+ HER2+, and TNBC groups, we found that patients in subtype 1 showed better prognosis in ER+ and PR+ groups (P < 0.05) but had no difference from prognosis of subtype 2 in HER2+ and TNBC groups. These findings may have implications in understanding of breast cancer and filtering effective therapeutic strategies for targeted therapy.