Cassoni Paola, Marrocco Tiziana, Sapino Anna, Allia Elena, Bussolati Gianni
Department of Biomedical Sciences and Human Oncology, University of Torino, Torino, Italy.
Int J Oncol. 2006 May;28(5):1263-8.
The role of the neurohypophyseal peptide oxytocin (OT) and its receptor (OTR) in the breast has been described mainly in relation to breast feeding or to neoplastic growth regulation. We demonstrate here the presence of OT synthesis within the breast under both physiological and neoplastic conditions. In order to clarify whether normal epithelial and myoepithelial cells could synthesize OT, the two different cell types were separated using immunomagnetic technique after enzymatic digestion of breast specimens obtained during reductive mastoplasty. The freshly isolated cells as well as primary stabilized cultures derived from purified normal breast epithelial and myopithelial cells were then studied. Both epithelial and myoepithelial cells contained the mRNA for OT and OTR; however, only myoepithelial cells showed an effective OT synthesis and detectable peptide release in the culture medium. Moreover, OT expression was studied at mRNA and protein level in 10 human breast carcinoma cell lines. OT mRNA was present in half (5 out of 10) of the breast carcinoma cell lines tested, and OT was synthesized and released in the cell medium, irrespective of the estrogen receptor status of the different cell lines. However, in the two ER+ cell lines actively producing OT, such synthesis was significantly increased following estradiol (E2) treatment. These data altogether suggest the existence of a local OT source within the normal as well as within the neoplastic breast, and that such synthesis can be modulated by E2.
神经垂体肽催产素(OT)及其受体(OTR)在乳腺中的作用,主要是在母乳喂养或肿瘤生长调节方面进行描述的。我们在此证明,在生理和肿瘤条件下乳腺内均存在OT合成。为了阐明正常上皮细胞和肌上皮细胞是否能够合成OT,在对缩乳术中获取的乳腺标本进行酶消化后,使用免疫磁珠技术分离了这两种不同的细胞类型。然后对新鲜分离的细胞以及源自纯化的正常乳腺上皮细胞和肌上皮细胞的原代稳定培养物进行了研究。上皮细胞和肌上皮细胞均含有OT和OTR的mRNA;然而,只有肌上皮细胞在培养基中显示出有效的OT合成和可检测到的肽释放。此外,在10个人类乳腺癌细胞系中对OT的表达进行了mRNA和蛋白质水平的研究。在所测试的乳腺癌细胞系中,有一半(10个中有5个)存在OT mRNA,并且无论不同细胞系的雌激素受体状态如何,OT均在细胞培养基中合成并释放。然而,在两个活跃产生OT的ER +细胞系中,雌二醇(E2)处理后这种合成显著增加。这些数据共同表明,在正常乳腺和肿瘤乳腺中均存在局部OT来源,并且这种合成可以被E2调节。