Molecular mechanisms of the progression of the pituitary tumor and the role of tissue remodeling factors

用17 β-雌二醇（E2）或儿茶酚-雌激素（4-OH E2）治疗可增加植入GH 3细胞的动物的血清催乳素水平和肿瘤大小。VEGF和碱性FGF以及IGF结合蛋白7（IGFBP 7）和stathmin（一种调节微管动力学的胞浆磷蛋白）的表达在肿瘤组织中增加。E2增加培养的GH 3细胞VEGF和IGFBP 7的表达。敲低IGFBP 7表达可刺激肿瘤VEGF表达，并降低肿瘤细胞的增殖。整合素B1簇和集落的形成受到抑制。生长抑素受体（SSTR）激动剂或IGFBP 7抑制VEGF表达，表明IGFBP 7可能是参与抑制肿瘤进展的靶分子。此外，生长抑素抑制ERK的磷酸化并诱导CDK抑制剂p27。E2通过雌激素受体α（ERα）诱导的MAP激酶激活被SSTR刺激抑制，E2处理下调SSTR 1表达。因此，SSTR 1在抑制ERα下的增殖信号通路中起关键作用。

Treatment with 17B-estradiol (E2) or catechol-estrogen (4-OH E2) increased the serum levels of prolactin and the size of tumor in the animals implanted with GH3 cells. The expressions of VEGF and basic FGF as well as IGF-binding protein 7 (IGFBP7) and stathmin, a cytosolic phosphoprotein that regulates microtubule dynamics increased in the tumor tissues. E2 increased VEGF and IGFBP7 expression in cultured GH3 cells. Knocking down IGFBP7 expression stimulated tumor VEGF expression and decreased the proliferation of tumor cells. The formation of integrin B1 cluster and colonies was suppressed. Somatostatin receptor (SSTR) agonist or IGFBP7 inhibited VEGF expression, suggesting that IGFBP7 may be a target molecule that is involved in the suppression of tumor progression. Furthermore, Somatostatin inhibited the phosphorylation of ERK and induced a CDK inhibitor, p27. E2-induced MAP kinase activation via the estrogen receptor a (ERα) was suppressed by SSTR stimulation and E2 treatment down-regulates SSTR1 expression. Thus, SSTR1 is a crucial role for inhibiting the signaling pathway of proliferation under ERα.