High-mobility group A2 gene expression is frequently induced in non-functioning pituitary adenomas (NFPAs), even in the absence of chromosome 12 polysomy
High-mobility group A2 gene expression is frequently induced in non-functioning pituitary adenomas (NFPAs), even in the absence of chromosome 12 polysomy
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DOI：
10.1677/erc.1.01049
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发表时间：
2005-12-01
影响因子：
3.9
通讯作者：
Larizza, L
中科院分区：
文献类型：
--
作者：
Pierantoni, GM;Finell, P;Larizza, L
高迁移率 A2 组 (HMGA2) 基因在良性肿瘤中起着至关重要的作用，在良性肿瘤中，该基因经常重排，而在恶性肿瘤中，该基因在 HMGA2 基因座没有结构修饰的情况下过度表达。通过先前对人催乳素分泌垂体腺瘤的荧光原位杂交 (FISH) 和逆转录酶 PCR 分析，我们检测到 HMGA2 基因的重排及其与激活表达相关的天然区域的扩增。这些数据表明 HMGA2 基因在人垂体催乳素瘤发展中的作用，因为它们与过度表达 HMGA2 基因的转基因小鼠中催乳素/生长激素腺瘤的出现一致。为了评估 HMGA2 在垂体肿瘤发生中更普遍的作用，我们研究了一组无功能垂体腺瘤 (NFPA) 中 HMGA2 的扩增和表达，这些垂体腺瘤占所有垂体腺瘤的 25%。我们提供的证据表明，在测试的 18 个 NFPA 肿瘤中，有 12 个表达 HMGA2，但与催乳素瘤不同，只有在两种情况下，该基因的上调可能与 HMGA2 基因座的扩增和/或重排有关。在表达和非表达 NFPA 中发现 12 号染色体剂量增加，证实这一单一事件不足以驱动 HMGA2 基因的激活。 12 号染色体多体性促进 HMGA2 结构不稳定的作用已得到证实，但通过三体性的机制在常见的二倍体 NFPA 中不如在通常的超二倍体泌乳素瘤中普遍。 FISH 分析和/或序列改变无法检测到的 HMGA2 基因的微重排可能导致 NFPA 亚型垂体腺瘤中 HMGA2 基因的上调。然而，不能排除在一些 NFPA 患者中 HMGA2 过度表达可能是由于与恶性肿瘤中 HMGA2 过度表达相同但主要仍未知的机制所致。
The high-mobility group A2 (HMGA2) gene has a critical role in benign tumors where it is frequently rearranged, and in malignant tumors, where it is overexpressed in the absence of structural modification of the HMGA2 locus. By previous fluorescence in situ hybridization (FISH) and reverse transcriptase PCR analyses on human prolactin-secreting pituitary adenomas we detected rearrangement of the HMGA2 gene and amplification of its native region associated with activated expression. These data indicated a role for the HMGA2 gene in the development of human pituitary prolactinomas, since they are consistent with the appearance of prolactin/growth hormone adenomas in transgenic mice overexpressing the HMGA2 gene. To assess a more general role for HMGA2 in pituitary oncogenesis, we investigated HMGA2 amplification and expression in a panel of non-functioning pituitary adenomas (NFPAs) which account for 25% of all pituitary adenomas. We provide evidence that out of 18 NFPA tumors tested, 12 expressed HMGA2, but, different from prolactinomas, only in two cases the upregulation of the gene could be associated with amplification and/or rearrangement of the HMGA2 locus. Increased dosage of chromosome 12 was found in the expressing and non-expressing NFPAs, confirming that this sole event is insufficient to drive up activation of the HMGA2 gene. A role for chromosome 12 polysomy to promote structural instability of HMGA2 is confirmed, but the mechanism via trisomy is less prevalent in the frequently diploid NFPAs than in the usually hyperdiploid prolactinomas. Micro-rearrangements of HMGA2 gene not detectable by FISH analysis and/or sequence alterations could contribute to upregulation of HMGA2 gene in pituitary adenomas of the NFPA subtype. However, it cannot be excluded that the HMGA2 overexpression may be due, in some NFPA patients, to the same, still mainly unknown, mechanisms responsible for HMGA2 overexpression in malignant neoplasias.