Ain K B, Taylor K D, Tofiq S, Venkataraman G
Thyroid Cancer Research Laboratory, Medical Service, Veterans Affairs Medical Center, Lexington, Kentucky 40511, USA.
J Clin Endocrinol Metab. 1997 Jun;82(6):1857-62. doi: 10.1210/jcem.82.6.4013.
Somatostatin (SRIH) analogs can suppress the proliferation of human differentiated thyroid carcinoma cell lines that express SRIH receptors (SSTRs) demonstrated by radioligand binding analysis. Five distinct human SSTR subtypes (hSSTR1-5) that bind native SRIH exhibit diverse affinities to a wide range of SRIH analogs. Reverse transcriptase-PCR amplification of ribonucleic acids (RNAs) obtained from normal thyroid tissues and nine human thyroid carcinoma cell lines, grown as monolayer cultures and xenograft tumors in nude mice, were used to discriminate expression of SSTR subtype messenger RNAs (mRNAs). The cell lines were derived from a follicular adenoma (KAK-1), two follicular carcinomas (MRO-87 and WRO-82), two papillary carcinomas (NPA87 and KAT-10), and four anaplastic thyroid carcinomas (DRO-90, ARO-81, KAT-4, and KAT-18). Most thyroid cancer cell line monolayers and xenografts expressed SSTR3 and SSTR5 mRNAs. SSTR1 expression was more varied between monolayers and xenografts, whereas SSTR2 mRNA was only faintly detectable at the most extreme resolution. SSTR4 mRNA was faintly positive in only one anaplastic carcinoma xenograft. Normal thyroid also expressed SSTR3 and SSTR5 mRNAs, with only faint expression of SSTR1 and SSTR2 mRNAs (in one of five and three of five samples, respectively). SSTR mRNA expression was dependent upon in vitro culture conditions, as xenograft SSTR mRNA expression tended to decrease compared to that in each respective monolayer culture. Characterization of SSTR subtype expression in human thyroid carcinomas may permit targeting of specific SRIH analogs to inhibit proliferation of differentiated and anaplastic thyroid carcinomas in patients.
生长抑素(SRIH)类似物可抑制人分化型甲状腺癌细胞系的增殖,放射性配体结合分析表明这些细胞系表达生长抑素受体(SSTRs)。与天然SRIH结合的五种不同的人SSTR亚型(hSSTR1 - 5)对多种SRIH类似物表现出不同的亲和力。从正常甲状腺组织以及九个在裸鼠中作为单层培养物和异种移植肿瘤生长的人甲状腺癌细胞系中获取的核糖核酸(RNAs),通过逆转录酶 - PCR扩增来鉴别SSTR亚型信使核糖核酸(mRNAs)的表达。这些细胞系源自一个滤泡性腺瘤(KAK - 1)、两个滤泡性癌(MRO - 87和WRO - 82)、两个乳头状癌(NPA87和KAT - 10)以及四个间变性甲状腺癌(DRO - 90、ARO - 81、KAT - 4和KAT - 18)。大多数甲状腺癌细胞系单层培养物和异种移植瘤表达SSTR3和SSTR5 mRNAs。SSTR1的表达在单层培养物和异种移植瘤之间差异更大,而SSTR2 mRNA在最高分辨率下仅能微弱检测到。SSTR4 mRNA仅在一个间变性癌异种移植瘤中呈微弱阳性。正常甲状腺也表达SSTR3和SSTR5 mRNAs,SSTR1和SSTR2 mRNAs表达微弱(分别在五个样本中的一个和五个样本中的三个)。SSTR mRNA表达取决于体外培养条件,因为与各自的单层培养相比,异种移植的SSTR mRNA表达往往会降低。对人甲状腺癌中SSTR亚型表达的特征分析可能有助于靶向特定的SRIH类似物,以抑制患者分化型和间变性甲状腺癌的增殖。