Ruebel Katharina H, Leontovich Alexey A, Jin Long, Stilling Gail A, Zhang Heyu, Qian Xiang, Nakamura Nobuki, Scheithauer Bernd W, Kovacs Kalman, Lloyd Ricardo V
Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN 55905, USA.
Endocrine. 2006 Jun;29(3):435-44. doi: 10.1385/ENDO:29:3:435.
Very few of the genes that are important in pituitary tumor initiation, progression, and metastasis have been identified to date. To identify potential genes that may be important in pituitary tumor progression and carcinoma development, we used Affymetrix GeneChip HGU-133A-oligonucleotide arrays, which contain more than 15,000 characterized genes from the human genome to study gene expression in an ACTH pituitary carcinoma metastatic to the liver and four pituitary adenomas. Reverse-transcriptase real-time quantitative- PCR (RT-qPCR) was then used to analyze 4 nonneoplastic pituitaries, 19 adenomas, and the ACTH carcinoma. A larger series of pituitary adenomas and carcinomas were also analyzed for protein expression using tissue microarrays (TMA) (n = 233) and by Western blotting (n = 18). There were 4298 genes that were differentially expressed among the adenomas compared to the carcinoma, with 2057 genes overexpressed and 2241 genes underexpressed in the adenomas. The beta-galactoside binding protein galactin-3 was underexpressed in some adenomas compared to the carcinomas. Prolactin (PRL) and ACTH tumors had the highest levels of expression of galectin-3. The human achaetescute homolog-1 ASCL1 (hASH-1) gene was also underexpressed in some adenomas compared to the carcinoma. Prolactin and ACTH tumors had the highest levels of expression of hASH-1. ID2, which has an important role in cell development and tumorigenesis, was underexpressed in some adenomas compared to the carcinomas. Transducin-like enhancer of split four/ Groucho (TLE-4) was over-expressed in adenomas compared to the ACTH carcinoma. The differential expression of these genes was validated by RT-qPCR, by immunohistochemistry using TMA and by Western blotting. These results indicate that the LGALS3, hASH1, ID2, and TLE-4 genes may have important roles in the development of pituitary carcinomas.
迄今为止，在垂体肿瘤的起始、进展和转移过程中发挥重要作用的基因很少被鉴定出来。为了确定可能在垂体肿瘤进展和癌发生中起重要作用的潜在基因，我们使用了Affymetrix GeneChip HGU - 133A寡核苷酸阵列，该阵列包含来自人类基因组的15000多个已鉴定基因，用于研究一例转移至肝脏的促肾上腺皮质激素（ACTH）垂体癌和4例垂体腺瘤中的基因表达。随后，采用逆转录实时定量聚合酶链反应（RT - qPCR）分析4例非肿瘤性垂体、19例腺瘤和ACTH癌。还使用组织微阵列（TMA）（n = 233）和蛋白质免疫印迹法（n = 18）对更大系列的垂体腺瘤和癌进行了蛋白质表达分析。与癌相比，腺瘤中有4298个基因差异表达，其中2057个基因在腺瘤中过表达，2241个基因在腺瘤中低表达。与癌相比，β - 半乳糖苷结合蛋白半乳凝素 - 3在一些腺瘤中低表达。催乳素（PRL）和ACTH肿瘤中半乳凝素 - 3的表达水平最高。人类无翅型MMTV整合位点家族成员1（ASCL1）基因（hASH - 1）与癌相比，在一些腺瘤中也低表达。催乳素和ACTH肿瘤中hASH - 1的表达水平最高。在细胞发育和肿瘤发生中起重要作用的ID2与癌相比，在一些腺瘤中低表达。与ACTH癌相比，转导素样分裂增强子4 / Groucho（TLE - 4）在腺瘤中过表达。这些基因的差异表达通过RT - qPCR、使用TMA的免疫组织化学和蛋白质免疫印迹法得到验证。这些结果表明，LGALS3、hASH1、ID2和TLE - 4基因可能在垂体癌的发生发展中起重要作用。
