Corbetta S, Ballaré E, Mantovani G, Lania A, Losa M, Di Blasio A M, Spada A
Ospedale Maggiore IRCCS, University of Milan, San Raffaele IRCCS, Via Francesco Sforza 35, 21022 Milan, Italy.
Eur J Clin Invest. 2001 Mar;31(3):208-14. doi: 10.1046/j.1365-2362.2001.00786.x.
The role of somatostatin receptor subtypes 2 and 5 (SSTR2 and SSTR5) in determining the secretory and proliferative phenotype as well as the sensitivity to somatostatin analogue treatment is not clearly established. We quantified the expression of SSTR2 and SSTR5 mRNA using a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 19 human growth hormone (GH) -secreting adenomas. Tumour characteristics and in vivo sensitivity to somatostatin analogues were assessed; tumours were screened for Gsalpha gene mutations. PCR products of SSTR2 and SSTR5 DNA from tumours resistant to somatostatin analogues were directly sequenced. All tumours expressed both SSTR2 and SSTR5 mRNA at variable levels. No significant correlation between SSTR2 and SSTR5 expression and the presence of Gsalpha mutation, GH levels, or tumour size and invasiveness was observed. A negative correlation between SSTR2 and SSTR5 mRNA levels was observed (r = 0.5; P < 0.05). No significant correlation between the levels of SSTR2 and SSTR5 expression and the in vivo responsiveness to somatostatin analogues was observed, although a tendency to a low SSTR2 expression in resistant tumours was found. No mutations in the coding or bordering regions of either SSTR2 or SSTR5 adenomatous DNA from patients totally or partially resistant to somatostatin analogues were found. The study shows that the different expression of SSTR2 and SSTR5 in GH-secreting adenomas is not significantly correlated with the secretory and proliferative phenotype, although the large, hypersecretory tumours and those with a poor sensitivity to somatostatin analogues seem to express low levels of SSTR2 mRNA. Moreover, both SSTR2 and SSTR5 DNA from tumours resistant to somatostatin analogues were found to possess intact coding sequences.
生长抑素受体亚型2和5（SSTR2和SSTR5）在决定分泌和增殖表型以及对生长抑素类似物治疗的敏感性方面所起的作用尚未明确。我们使用半定量逆转录-聚合酶链反应（RT-PCR）对19例分泌人生长激素（GH）的腺瘤中SSTR2和SSTR5 mRNA的表达进行了定量。评估了肿瘤特征和对生长抑素类似物的体内敏感性；对肿瘤进行了Gsalpha基因突变筛查。对生长抑素类似物耐药的肿瘤的SSTR2和SSTR5 DNA的PCR产物进行直接测序。所有肿瘤均以不同水平表达SSTR2和SSTR5 mRNA。未观察到SSTR2和SSTR5表达与Gsalpha突变的存在、GH水平、肿瘤大小或侵袭性之间存在显著相关性。观察到SSTR2和SSTR5 mRNA水平之间呈负相关（r = 0.5；P < 0.05）。尽管在耐药肿瘤中发现有SSTR2表达降低的趋势，但未观察到SSTR2和SSTR5表达水平与对生长抑素类似物的体内反应性之间存在显著相关性。在对生长抑素类似物完全或部分耐药的患者的腺瘤性DNA的SSTR2或SSTR5的编码或边界区域未发现突变。该研究表明，分泌GH的腺瘤中SSTR2和SSTR5的不同表达与分泌和增殖表型无显著相关性，尽管大的、高分泌性肿瘤以及那些对生长抑素类似物敏感性差的肿瘤似乎表达低水平的SSTR2 mRNA。此外，发现对生长抑素类似物耐药的肿瘤的SSTR2和SSTR5 DNA均具有完整的编码序列。
