Enriori Pablo J, Vázquez Stella Maris, Chiauzzi Violeta, Pérez Cecilia, Fischer Carlos R, Gori Jorge R, Etkin Alberto E, Charreau Eduardo, Calandra Ricardo S, Lüthy Isabel A
Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
Clin Endocrinol (Oxf). 2006 Jan;64(1):20-8. doi: 10.1111/j.1365-2265.2005.02408.x.
Gross cystic disease (GCD) of the breast is reported to occur in 7% of women in the developed world and, although not premalignant, is thought to be associated with an increased risk of breast cancer. Hormone and growth factor concentration levels were measured in breast cyst fluid (BCF) to correlate them with their mitogenic activity in tumour (MCF-7) or nontransformed (MCF-10A) cells.
Oestradiol (E2), oestrone (E1), E2-sulfate (E2-S), E1-sulfate (E1-S) and epidermal growth factor (EGF) concentrations were, as expected, significantly higher in type I than in type II cysts, while transforming growth factor-beta 2 (TGF-beta2) showed higher levels in type II cysts. Fifty per cent of the BCF samples stimulated [3H]-thymidine incorporation into MCF-7 cells while 34.5% inhibited this parameter. In MCF-10A cells, most BCF samples were stimulatory (85%). E2, E1 and EGF concentrations in BCF samples correlated significantly and positively with cell proliferation in MCF-7 cells, whereas a significant negative correlation was found for TGF-beta2. In MCF-10A cells, only E2-S and E1-S exhibited significant positive correlation, whereas a significant negative correlation was found for TGF-beta2. Progesterone (Pg), E2 and EGF incubated under the same conditions had a stimulatory effect on [3H]-thymidine incorporation into MCF-7 cells, whereas TGF-beta2 inhibited this parameter. Pg, E2, E1 and EGF significantly stimulated this parameter in MCF-10A cells.
The stimulatory action of BCF on cell proliferation in a model of human breast epithelial cells could partly explain the increased incidence of breast cancer in cyst-bearing women.
据报道,在发达国家,7%的女性患有乳腺大囊性病(GCD),尽管它并非癌前病变,但被认为与乳腺癌风险增加有关。对乳腺囊肿液(BCF)中的激素和生长因子浓度水平进行了测量,以将它们与其在肿瘤(MCF - 7)或未转化(MCF - 10A)细胞中的促有丝分裂活性相关联。
正如预期的那样,I型囊肿中的雌二醇(E2)、雌酮(E1)、E2 - 硫酸盐(E2 - S)、E1 - 硫酸盐(E1 - S)和表皮生长因子(EGF)浓度显著高于II型囊肿,而转化生长因子 - β2(TGF - β2)在II型囊肿中的水平较高。50%的BCF样本刺激[³H] - 胸腺嘧啶核苷掺入MCF - 7细胞,而34.5%的样本抑制该参数。在MCF - 10A细胞中,大多数BCF样本具有刺激作用(85%)。BCF样本中的E2、E1和EGF浓度与MCF - 7细胞中的细胞增殖显著正相关,而TGF - β2则呈显著负相关。在MCF - 10A细胞中,只有E2 - S和E1 - S表现出显著正相关,而TGF - β2呈显著负相关。在相同条件下孵育的孕酮(Pg)、E2和EGF对[³H] - 胸腺嘧啶核苷掺入MCF - 7细胞有刺激作用,而TGF - β2抑制该参数。Pg、E2、E1和EGF在MCF - 10A细胞中显著刺激该参数。
BCF对人乳腺上皮细胞模型中细胞增殖的刺激作用可能部分解释了患囊肿女性乳腺癌发病率增加的原因。