Regulation of Fatty Acid Synthetase Ribonucleic Acid in the Human Endometrium during the Menstrual Cycle*

Escot, Chantal; Joyeux, Christian; Mathieu, Michel; Maudelondé, Thierry; Pagès, A; Rochefort, Henri; Chalbos, Dany

doi:10.1210/jcem-70-5-1319

Cited by 19 publications

(9 citation statements)

References 16 publications

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“…During the menstrual cycle, the expression of FASN in the human endometrium is closely linked to the expression of the proliferation antigen Ki-67, ER, and PR, suggesting a connection between FASN and the E 2 /ER-dependent signaling in endometrial cell proliferation. Thus, FASN expression increases in endometrial glands and stromal cells from the proliferative to the early secretory phase, and after cessation of cell proliferation in the mid-to the late-secretory phase, the endometrial tissue becomes FASN negative (43,44). In normal mammary glands, the stimulation of FASN at lactation is considered to be due to stimulatory effects of cortisol, prolactin, and insulin, facilitated by decreased production of progesterone.…”

Section: Hormonal Regulation Of Fasn In Hormone-sensitive Carcinomasmentioning

confidence: 99%

Targeting Fatty Acid Synthase in Breast and Endometrial Cancer: An Alternative to Selective Estrogen Receptor Modulators?

2006

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There is an urgent need to identify and develop a new generation of therapeutic agents and systemic therapies targeting the estradiol (E2)/estrogen receptor (ER) signaling in breast cancer. In this regard, new information on the mechanisms of E2/ER function and/or cross talk with other prosurvival cascades should provide the basis for the development of other ideal anti-E2 therapies with the intent to enhance clinical efficacy, reduce side effects or both. Our very recent assessment of the mechanisms by which cancer-associated increased lipogenesis and its inhibition alters the E2/ER signaling discovered that fatty acid synthase (FASN), the enzyme catalyzing the terminal steps in the de novo biosynthesis of long-chain fatty acids, differentially modulates the state of sensitivity of breast and endometrial cancer cells to E2-stimulated ER transcriptional activation and E2-dependent cell growth and survival: 1) pharmacological inhibition of FASN activity induced a dramatic augmentation of E2-stimulated ER-driven gene transcription, whereas interference (RNAi)-mediated silencing of FAS gene expression drastically lowered E2 requirements for optimal activation of ER transcriptional activation in breast cancer cells; conversely, pharmacological and RNAi-induced inhibition of FASN worked as an antagonist of E2- and tamoxifen-dependent ER transcriptional activity in endometrial adenocarcinoma cells; 2) pharmacological and RNAi-induced inhibition of FASN synergistically enhanced E2-mediated down-regulation of ER protein and mRNA expression in breast cancer cells, whereas specific FASN blockade resulted in a marked down-regulation of E2-stimulated ER expression in endometrial cancer cells; and 3) FASN inhibition decreased cell proliferation and cell viability by promoting apoptosis in hormone-dependent breast and endometrial cancer cells. In this review we propose that, through a complex mechanism involving the regulation of MAPK/ER cross talk as well as critical E2-related proteins including the Her-2/neu (erbB-2) oncogene and the cyclin-dependent kinase inhibitors p21(WAF1/CIP1) and p27(Kip1), a previously unrevealed connection exists between FASN and the genomic and nongenomic ER activities in breast and endometrial cancer cells. From a clinical perspective, we suggest that if chemically stable FASN inhibitors or cell-selective systems able to deliver RNAi targeting FASN gene demonstrate systemic anticancer effects of FASN inhibition in vivo, additional preclinical studies to characterize their anti-breast cancer actions should be of great interest as the specific blockade of FASN activity may also provide a protective means against endometrial carcinoma associated with tamoxifen-based breast cancer therapy.

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Section: Hormonal Regulation Of Fasn In Hormone-sensitive Carcinomasmentioning

confidence: 99%

Targeting Fatty Acid Synthase in Breast and Endometrial Cancer: An Alternative to Selective Estrogen Receptor Modulators?

2006

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“…Most tissues, except for the liver, adipose tissue, cycling endometrium (5), fetal lungs (6), lactating breast (7,8) and embryos (3,9) utilize dietary FAs to build new structural lipids. Therefore, FAS is expressed at low levels in most normal tissues.…”

Section: Introductionmentioning

confidence: 99%

High overexpression of fatty acid synthase is associated with poor survival in Chinese patients with gastric carcinoma

Hou

Fei

Qin

et al. 2012

Experimental and Therapeutic Medicine

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Fatty acid synthase (FAS) is the key enzyme regulating de novo biosynthesis of fatty acids. FAS overexpression has been found in many types of tumors and is associated with poor survival. However, the expression of FAS and its relationship with prognosis in Chinese patients with gastric carcinoma are still unknown. Therefore, in this study, we examined the expression of FAS using tissue microarrays and determined its correlation with clinicopathological characteristics and prognosis of gastric carcinoma in Chinese patients. FAS overexpression was graded as S (T/A) <1, ≥1 to <2, ≥2 to <3 or ≥3 in 35 (38.9%), 20 (22.2%), 9 (10%) and 26 (28.9%) patients, respectively. High FAS overexpression [S (T/A) ≥3] was significantly correlated with poor prognosis (log-rank test, P= 0.0078) and with decreased 3-year survival rate (χ2 test, P=0.0023). FAS overexpression was not significantly associated with other clinicopathological characteristics. In conclusion, our results suggest that FAS expression might be a potential prognostic marker for gastric carcinoma in Chinese patients.

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“…Exceptions include the liver [9], adipose tissue [10], cycling endometrium [11], foetal lung with the biosynthesis of lecithin [12] and lactating mammary gland [13,14].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Fatty Acid Synthase in Oesophageal Squamous Cell Dysplasia and Carcinoma

Nemoto¹,

Terashima²,

Kogure³

et al. 2001

Pathobiology

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Objective: The expression of fatty acid synthase (FAS), an enzyme necessary for de novo fatty acid synthesis, has been examined in several types of tumours so far, but not in oesophageal cancer and dysplasia. Methods: We examined the immunohistochemical reactivity of FAS in 4 normal adult oesophagi, 14 dysplastic oesophageal lesions, and 80 squamous cell carcinomas and 6 cases with 4 special types of malignancies of the oesophagus. We also analysed the correlation between FAS expression and various clinicopathological features and long-term survival in patients with oesophageal cancer. Results: In the normal oesophagus, only faint cytoplasmic FAS expression was observed in cells of the basal layer. In contrast, FAS-positive cells were found in 92.9% of cases of dysplasia and 96.5% of cases of carcinoma including 6 cases with a specific histological subtype. However, high expression of FAS did not correlate with either clinicopathological features or prognosis of patients with oesophageal cancer. Conclusion: Our results demonstrate that FAS is expressed in almost all oesophageal carcinomas of both usual and special types and dysplastic lesions, suggesting that FAS may be upregulated continuously from the early stage of oesophageal squamous cell carcinogenesis to established carcinoma.

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Regulation of Fatty Acid Synthetase Ribonucleic Acid in the Human Endometrium during the Menstrual Cycle*

Cited by 19 publications

References 16 publications

Targeting Fatty Acid Synthase in Breast and Endometrial Cancer: An Alternative to Selective Estrogen Receptor Modulators?

Targeting Fatty Acid Synthase in Breast and Endometrial Cancer: An Alternative to Selective Estrogen Receptor Modulators?

High overexpression of fatty acid synthase is associated with poor survival in Chinese patients with gastric carcinoma

Overexpression of Fatty Acid Synthase in Oesophageal Squamous Cell Dysplasia and Carcinoma

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