Effect of breast cyst fluid and its constituents on oestrogen metabolism in breast cancer cell lines
Başlık çevirisi mevcut değil.
- Tez No: 400124
- Danışmanlar: DR. LESLİE LAİ, DR. A. W. SKİLLEN
- Tez Türü: Doktora
- Konular: Biyokimya, Biochemistry
- Anahtar Kelimeler: Belirtilmemiş.
- Yıl: 1999
- Dil: İngilizce
- Üniversite: University of Newcastle upon Tyne
- Enstitü: Yurtdışı Enstitü
- Ana Bilim Dalı: Belirtilmemiş.
- Bilim Dalı: Belirtilmemiş.
- Sayfa Sayısı: 276
Özet
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Özet (Çeviri)
Gross cystic breast disease (GCBD) is the most common benign disease ofbreast which may be associated with 2 to 4.4 times higher risk of breast cancer.There are two groups of breast cyst: lined by apocrine metaplastic epithelium(Na/K < 3, high risk) or flattened epithelium (Na/K > 3, low risk).The aims were: 1) Assess the effect of BCF on growth of, and oestronesulphatase activity in, breast cancer cell lines. 2) Measure concentrations of TGF-b2, IGF-I, IGF-II, IGFBP-3 and PSA in the 2 subgroups of breast cysts. 3) The neteffect of GCDFP-15, -24, TGF-b2, and PSA on oestrogen metabolism in breastcancer cell lines was studied. 4) The latent forms of TGF-b2 in BCF wereinvestigated.MCF-7 and MDA-MB-231 cell growth were significantly inhibited byBCF. Oestrone sulphatase activity was significantly inhibited in the MCF-7 cellswhile significant stimulation of oestrone sulphatase activity was observed inMDA-MB-231 cells by BCF. TGF-b2 concentrations were found to besignificantly higher in the low risk group. High concentrations of TGF-b2significantly inhibited oestrone sulphate (E1S) to oestrone (E1) and E1 to oestradiol(E2) conversion in the MCF-7 cell line. Both GCDFP-15 and 24, either separatelyor together, had no significant effect on cell growth and interconversion of E1 toE2 in the MCF-7 cell line. The concentrations of IGF-I, IGF-II and IGFBP-3 weresignificantly higher in the low risk group than high risk group. PSA levels in thehigh and low risk groups were not significantly different while low concentrationsof PSA were found to inhibit MCF-7 cell growth and to stimulate the conversionof E2 to less potent oestrogen E1. PSA had no effect on the MDA-MB-231 cellline.The presence of endogenous sulphatase inhibitory substances in BCF isimportant because of the therapeutic potential of sulphatase inhibition. Thesignificantly higher concentrations of TGF-b2 in the high risk group may explainthe lower risk of breast cancer in this group of women. The significantly higherconcentrations of IGF-I, IGF-II and IGFBP-3 in the high risk group may explainthe lack of increased mitogenic effect, as TGF-b may regulate the production ofIGFBP-3 in this group. PSA may be a negative growth regulator of hormonedependentbreast cancers.
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