Luparello C, Santamaria F, Schilling T
Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Palermo, Viale delle Scienze, Italy.
Biol Chem. 2000 Apr;381(4):303-8. doi: 10.1515/BC.2000.039.
It was previously reported that 8701-BC breast tumour cells express the gene for parathyroid hormone-related peptide (PTHrP) and PTH/PTHrP receptor (PTHrP-R) and release immunoreactive PTHrP (iPTHrP) into the extracellular medium. Since the regulation of PTHrP and PTHrP-R by breast cancer cells has been poorly investigated so far, we have chosen the 8701-BC cell line as a model system to investigate whether alterations in the extracellular Ca2+ concentration ([Ca2+]e) and treatment with some well-known differentiation agents for breast cells, such as dimethyl sulfoxide, hydrocortisone, progesterone, prolactin, all-trans retinoic acid and transforming growth factor-beta1 might (i) modulate quantitatively the release of iPTHrP, (ii) affect the PTHrP promoter usage and mRNA splicing patterns, and (iii) modify the expression of PTHrP-R. The data obtained indicate that 8701-BC cells are potentially able to utilise different start sites and mRNA splicing patterns for PTHrP transcription, and respond to variations of [Ca2+]e and to the addition of two hormones, hydrocortisone and progesterone, with modifications in the extracellular amount of iPTHrP. Moreover, expression of PTHrP-R is also modulated by changes of [Ca2+]e or treatment with hydrocortisone. This indicates that the 8701 -BC cell line is a suitable in vitro model for further studies on the complex molecular regulation of the PTHrP/PTHrP-R pair in breast cancer.
先前有报道称，8701 - BC乳腺癌细胞表达甲状旁腺激素相关肽（PTHrP）基因和PTH/PTHrP受体（PTHrP - R），并将免疫反应性PTHrP（iPTHrP）释放到细胞外培养基中。由于迄今为止对乳腺癌细胞对PTHrP和PTHrP - R的调节研究甚少，我们选择8701 - BC细胞系作为模型系统，以研究细胞外Ca2 +浓度（[Ca2 +] e）的变化以及用一些著名的乳腺癌细胞分化诱导剂（如二甲基亚砜、氢化可的松、孕酮、催乳素、全反式维甲酸和转化生长因子 - β1）处理是否会（i）定量调节iPTHrP的释放，（ii）影响PTHrP启动子的使用和mRNA剪接模式，以及（iii）改变PTHrP - R的表达。所获得的数据表明，8701 - BC细胞可能能够利用不同的起始位点和mRNA剪接模式进行PTHrP转录，并对[Ca2 +] e的变化以及添加氢化可的松和孕酮这两种激素作出反应，导致细胞外iPTHrP量发生改变。此外，PTHrP - R的表达也受到[Ca2 +] e变化或氢化可的松处理的调节。这表明8701 - BC细胞系是用于进一步研究乳腺癌中PTHrP/PTHrP - R对复杂分子调节的合适体外模型。
