Immunohistochemical detection of FAS was associated with morphological features of the tumors, with immunohistochemical expression of c-erbB-2, cathepsin D, estrogen and progesterone receptor status and with DNA ploidy in order to detect a statistical correlation.
In 17% of the cases, FAS protein levels were high despite low mRNA levels, and these tumors exhibited a distinct molecular signature when compared with tumors that did not express FAS protein.
Inhibition of tumor-associated fatty acid synthase hyperactivity induces synergistic chemosensitization of HER -2/ neu -overexpressing human breast cancer cells to docetaxel (taxotere).
We designed our experiments to evaluate whether fatty acid synthase (FAS), a lipogenic enzyme linked to tumor virulence in population studies of human cancer, is necessary for the malignant transformation induced by Her-2/neu (erbB-2) oncogene, which is overexpressed not only in invasive breast cancer but also in premalignant atypical duct proliferations and in ductal carcinoma in situ of the breast.
In this report, we demonstrate that the expression of the tumor suppressor gene PTEN has a significant inverse correlation with FAS expression in the case of prostate cancer in the clinical setting, and inhibition of the PTEN gene leads to the overexpression of FAS in vitro.
Sterol response element-binding protein-1c (SREBP-1c) is required for induction of lipogenesis-related genes, including S14 and fatty acid synthase (FAS), in hepatocytes, and correlation of SREBP-1c and FAS expression suggested that SREBP-1c drives lipogenesis in tumors as well.
Marked (2+) FASN overexpression was observed in 110 (11%) of the 976 tumors and was significantly more common in MSI-H tumors (21% [28/135]) than MSI-low (5.6% [4/72], P = .004) and MSS tumors (11% [72/678], P = .001).
Tumor-associated fatty acid synthase (FAS) is implicated in tumorigenesis and connected to HER2 (human epidermal growth factor receptor 2) by systemic analyses.
Together these findings reveal a wide network of pathways that are influenced in response to FAS knockdown and provide new insight into the role of this enzyme in tumor cell survival and proliferation.
Tumors located on the left side of the colon showed higher levels of FAS activity and tumors from male patients showed higher FAS activity than tumors from females.
We previously reported that pharmacological and RNA interference-induced inhibition of tumor-associated fatty acid synthase (FASN; Oncogenic antigen-519), a key metabolic enzyme catalyzing the synthesis of long-chain saturated fatty acids, drastically down-regulates HER2 expression in human breast cancer cells bearing HER2 gene amplification.
Tumour-associated FASN, by conferring growth and survival advantages rather than functioning as an anabolic energy-storage pathway, appears to necessarily accompany the natural history of most human cancers.
Conversely, Fatty acid synthase (FAS) enzyme, required for the synthesis of fatty acids, is found over-expressed in tumors and inhibition of FAS triggers apoptosis in human cancer cells.
In addition, our results of immunohistochemical analysis for human breast tumor specimens indicate that the expressions of both FAS and SREBP-1 were colocalized with hypoxic regions in the tumors.
These findings indicate that suppression of palmitate synthesis is not sufficient for eliciting tumor cell death and suggest that the unique effect of inhibition of FAS results from negative regulation of the mTOR pathway via DDIT4.
Cav-1 and FASN expression correlated predominantly with clinical characteristics, such as histologic grade and advanced tumor stage (e.g., high Cav-1 and FASN expression correlated with poor differentiation status) and a significant survival advantage was found in patients with low co-expressing FASN and Cav-1 tumors.
Forced expression of FASN in iPrECs, AR-iPrECs, and LNCaP cells increased cell proliferation and soft agar growth. iPrECs that expressed both FASN and androgen receptor (AR) formed invasive adenocarcinomas in immunodeficient mice (12 of 14 mice injected formed tumors vs 0 of 14 mice injected with AR-iPrEC expressing empty vector (P < .001, Fisher exact test); however, iPrECs that expressed only FASN did not.
In multivariate analysis, AURKA was associated with cyclin D1 expression (P = .010) and inversely with PIK3CA mutation (P=.014), fatty acid synthase expression (P=.028), and family history of colorectal cancer (P = .050), but not with sex, age, body mass index, tumor location, stage, CIMP, MSI, KRAS, BRAF, BMI, LINE-1 hypomethylation, p53, p21, beta-catenin, or cyclooxygenase 2.