Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Organochlorine industrial compounds, combustion products and pesticides have been widely identified in the environment and residues have been detected in extracts prepared from fish, wildlife, human tissues as well as human milk and serum. Many of these compounds possess sex steroid activities and therefore have the potential to disrupt endocrine-regulated homeostasis. Organochlorines which exhibit hormonal activity include: (i) polychlorinated biphenyls (PCBs), hydroxylated PCBs, o,p'-DDT, and other organochlorine insecticides which exhibit estrogen receptor (ER) agonist activities; (ii) p,p'-DDE, a ligand for the androgen receptor which exhibits antiandrogen activity; (iii) PCBs, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and related aromatic hydrocarbons which bind the aryl hydrocarbon (Ah) receptor and exhibit tissue-specific antiestrogenic activity; and (iv) hydroxylated aromatics which bind transthyretin, a thyroid hormone binding protein. Although, it has been suggested that the estrogenic activity of PCBs and DDE may be a contributing factor for development of breast cancer in women, levels of these compounds are not consistently elevated in breast cancer patients and there is no evidence that women occupationally-exposed to relatively high levels of PCBs or DDE exhibit an increased incidence of breast cancer. In contrast, epidemiology studies suggest that women exposed to high levels of TCDD during an industrial accident in Seveso, Italy, have a decreased incidence of both breast and endometrial cancer. Based on the dietary intake of hormone or antihormone mimics derived from natural compounds in food, the estrogenic contribution of organochlorine compounds is small and their role in development of breast cancer is questionable.
 ...
PMID:Organochlorine exposure and risk for breast cancer. 910 95

Several anthropogenous and naturally occurring substances, referred to as estrogen active compounds (EACs), are able to interfere with hormone and in particular estrogen receptor signaling. EACs can either cause adverse health effects in humans and wildlife populations or have beneficial effects on estrogen-dependent diseases. The aim of this study was to examine global gene expression profiles in estrogen receptor (ER)-proficient Ishikawa plus and ER-deficient Ishikawa minus endometrial cancer cells treated with selected well-known EACs (diethylstilbestrol, genistein, zearalenone, resveratrol, bisphenol A and o,p'-DDT). We also investigated the effect of the pure antiestrogen ICI 182,780 (ICI) on the expression patterns caused by these compounds. Transcript levels were quantified 24 h after compound treatment using Illumina BeadChip Arrays. We identified 87 genes with similar expression changes in response to all EAC treatments in Ishikawa plus. ICI lowered the magnitude or reversed the expression of these genes, indicating ER dependent regulation. Apart from estrogenic gene regulation, bisphenol A, o,p'-DDT, zearalenone, genistein and resveratrol displayed similarities to ICI in their expression patterns, suggesting mixed estrogenic/antiestrogenic properties. In particular, the predominant antiestrogenic expression response of resveratrol could be clearly distinguished from the other test compounds, indicating a distinct mechanism of action. Divergent gene expression patterns of the phytoestrogens, as well as weaker estrogenic gene expression regulation determined for the anthropogenous chemicals bisphenol A and o,p'-DDT, warrants a careful assessment of potential detrimental and/or beneficial effects of EACs. The characteristic expression fingerprints and the identified subset of putative marker genes can be used for screening chemicals with an unknown mode of action and for predicting their potential to exert endocrine disrupting effects.
 ...
PMID:Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. 1937 25