Oyesiku N M, Evans C O, Brown M R, Blevins L S, Tindall G T, Parks J S
Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Clin Endocrinol Metab. 1997 Dec;82(12):4184-8. doi: 10.1210/jcem.82.12.4436.
Mutant, guanosine triphosphatase-deficient, alpha-subunits of the G protein, Gs, gsp ocogene have been discovered in 40% of GH-secreting pituitary adenomas. Therefore, we hypothesized that a novel G protein class, G alpha q, involved in pituitary signal transduction, might be involved in pituitary tumorigenesis. Recombinant mutations of G alpha q result in constitutive activation of phospholipase C and have transforming activity. Therefore, we screened tumor samples from 37 pituitary adenomas for the presence of activating mutations of the G alpha q gene. Importantly, our sample contains 8 FSH and LH adenomas. In the pituitary gland, FSH and LH are linked to the GnRH-G alpha q signaling cascade, making these tumors a logical choice for screening for G alpha q mutations. Complementary DNA (cDNA) was synthesized by RT-PCR with G alpha q specific primers to exclude pseudogene transcripts. Fragments of G alpha q cDNA-encompassing residues (Arg183, Gln209) were screened by single-strand conformation polymorphism and then sequenced in both directions. No mutations were detected. We conclude that mutations in these regions of the G alpha q cDNA occur infrequently, if at all, in human pituitary adenomas. Alternative mechanisms underlying pituitary tumorigenesis should be explored.
在40%的分泌生长激素的垂体腺瘤中发现了G蛋白Gs的突变型、鸟苷三磷酸酶缺陷型α亚基以及gsp癌基因。因此，我们推测一种参与垂体信号转导的新型G蛋白Gαq可能与垂体肿瘤发生有关。Gαq的重组突变会导致磷脂酶C的组成性激活并具有转化活性。因此，我们对37例垂体腺瘤的肿瘤样本进行了Gαq基因激活突变的筛查。重要的是，我们的样本包含8例促卵泡激素（FSH）和促黄体生成素（LH）腺瘤。在垂体中，FSH和LH与促性腺激素释放激素 - Gαq信号级联相关，这使得这些肿瘤成为筛查Gαq突变的合理选择。通过逆转录聚合酶链反应（RT-PCR）使用Gαq特异性引物合成互补DNA（cDNA），以排除假基因转录本。通过单链构象多态性筛选包含残基（Arg183、Gln209）的Gαq cDNA片段，然后进行双向测序。未检测到突变。我们得出结论，在人类垂体腺瘤中，Gαq cDNA这些区域的突变即使存在也很少见。应探索垂体肿瘤发生的其他潜在机制。
