Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer is a serious illness affecting approximately one in nine women in the United States. Although an actual cause for breast cancer is unknown, genetic and environmental factors have been associated with its onset. Elevated levels of estrogen and heightened expression of the WNT10B proto-oncogene have been implicated in the development of human malignant breast tumors because they enhance the proliferation of mammary tissue. Two pyrethroid insecticides, sumithrin and fenvalerate, have been shown to mimic estrogenic activity in MCF-7 human breast carcinoma cells by inducing pS2 expression whereas two other pyrethroids, permethrin and d-trans allethrin do not have the same capability. To investigate if estrogen and these four pyrethroid insecticides could affect the expression of a gene related to mammary gland development, WNT10B expression in pyrethroid-treated MCF-7 cells was examined. MCF-7 cells under normal growth conditions do not express WNT10B. Reverse-transcriptase polymerase chain reaction (RT-PCR), nested PCR and Southern hybridization were employed to detect WNT10B expression. As controls, cells were treated with either ethanol, corn oil, or Vista LPA solvent. When compared to the solvent-treated controls, sumithrin, fenvalerate and estrogen treated MCF-7 cells all had increased levels of WNT10B expression. The non-estrogenic pyrethroids, d-trans allethrin and permethrin, demonstrated a similar elevation of WNT10B expression at a lower concentration, but not at the higher concentration. The results suggest that pyrethroid insecticides and estrogen can enhance the expression of the WNT10B proto-oncogene. However, since both the estrogenic and non-estrogenic substances amplified Wnt10B expression, the mechanism likely involves multiple distinct pathways.
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PMID:Effects of pyrethroid insecticides and estrogen on WNT10B proto-oncogene expression. 1243 93

Approximately 60% of all breast tumors are estrogen-responsive and chemicals that show estrogenic or anti-estrogenic properties are able to interact with breast tumor growth. In a breast tumor, adipose stromal cells (fibroblasts) surrounding the epithelial tumor contain the aromatase enzyme, which converts androgens into estrogens. Exposure to aromatase inducers can therefore lead to increased estrogen levels and possibly to accelerated breast tumor growth. Subsequently, breast tumor cells synthesize and secrete elevated levels of factors such as prostaglandin E2 (PGE2), interleukin-6 (IL-6), and IL-6 soluble receptor (IL-6sR), which in turn have the ability to stimulate aromatase gene transcription in fibroblasts, establishing a positive feedback loop. In this study, a technique that allows for culturing MCF-7 epithelial breast tumor cells and healthy primary human mammary fibroblasts together in one compartment was developed. To establish the positive feedback loop, the co-culture was exposed to estrogenic compounds. RNA was isolated and reverse-transcriptase polymerase chain reaction (RT-PCR) was performed on the aromatase and pS2 genes. Exposure of the co-culture to estradiol (E2), diethylstilbestrol (DES), and bisphenol-A (BPA), resulted in a three- to seven-fold increase of pS2 transcription levels. Furthermore, pS2 transcription levels increased even more when the aromatase substrate testosterone (20 nM) was present in the co-culture medium. Exposure of the co-culture to the aromatase inducer dexamethasone (DEX) resulted in increased pS2 transcription levels, as well as increased aromatase transcription levels. Simultaneous exposure to DEX and the synthetic anti-estrogen ICI 182,780 almost completely blocked the pS2 response. The aromatase induction response was not altered by ICI 182,780 treatment. Simultaneous exposure to DEX and the non-steroidal aromatase inhibitor fadrozole, abolished the effect of the presence of testosterone in the co-culture medium, but did not result in pS2 gene transcription levels as low as seen after exposure to ICI 182,780. These observations indicate the presence of a positive feedback loop in our co-culture system. This co-culture provides a more sophisticated and sensitive system to detect direct and indirect estrogenic effects of compounds and their possible effects on breast tumor promotion.
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PMID:Co-culture of primary human mammary fibroblasts and MCF-7 cells as an in vitro breast cancer model. 1552 92