Loss of expression of GADD45 gamma, a growth inhibitory gene, in human pituitary adenomas: implications for tumorigenesis.
Loss of expression of GADD45 gamma, a growth inhibitory gene, in human pituitary adenomas: implications for tumorigenesis.
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DOI：
10.1210/jcem.87.3.8315
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发表时间：
2002-03
期刊：
影响因子：
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通讯作者：
Xun Zhang;Huiping Sun;D. Danila;S. R. Johnson;Yunli Zhou;B. Swearingen;A. Klibanski
中科院分区：
文献类型：
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作者：
Xun Zhang;Huiping Sun;D. Danila;S. R. Johnson;Yunli Zhou;B. Swearingen;A. Klibanski
在大多数人类垂体瘤中，潜在的分子致病机制仍然未知。GADD 45 γ是生长停滞和DNA损伤诱导基因家族的成员，其在细胞生长的负调控中起作用。我们已经发现，GADD 45 γ基因的mRNA表达是显着不同的正常人垂体组织和临床无功能垂体腺瘤，使用cDNA代表性差异分析。虽然GADD 45 γ mRNA在正常人垂体组织中被发现，但通过RT-PCR仅在18例临床无功能垂体瘤中的1例中检测到。此外，该基因在大多数GH或PRL分泌型垂体瘤中不表达（分别为6/8和7/10）。在集落形成试验中，将人GADD 45 γ cDNA转染入人垂体瘤衍生细胞系PDFS中，导致细胞生长急剧下降88%。GADD 45 γ还分别减少了其他垂体肿瘤衍生细胞系AtT 20和GH4中的集落形成约60%和50%，证实了其在控制垂体中细胞增殖中的功能。这些数据表明，GADD 45 γ是一个强大的生长抑制剂控制垂体细胞增殖，GADD 45 γ代表了第一个确定的基因，其表达在大多数人垂体肿瘤丢失。
The underlying molecular pathogenic mechanisms remain unknown in the majority of human pituitary tumors. GADD45 gamma is a member of a growth arrest and DNA damage-inducible gene family that functions in the negative regulation of cell growth. We have found that the mRNA expression of the GADD45 gamma gene is significantly different between normal human pituitary tissue and clinically nonfunctioning pituitary adenomas using cDNA-representational difference analysis. Although GADD45 gamma mRNA was found in normal human pituitary tissue, it was detectable in only 1 of 18 clinically nonfunctioning pituitary tumors by RT-PCR. Furthermore, this gene was not expressed in the majority of GH- or PRL-secreting pituitary tumors (6 of 8 and 7 of 10, respectively). In colony formation assays, transfection of human GADD45 gamma cDNA into the human pituitary tumor-derived cell line, PDFS, results in a dramatic decrease in cell growth by 88%. GADD45 gamma also reduces colony formation in other pituitary tumor-derived cell lines, AtT20 and GH4, by approximately 60% and 50%, respectively, confirming its function in controlling cell proliferation in the pituitary. These data indicate that GADD45 gamma is a powerful growth suppressor controlling pituitary cell proliferation, and GADD45 gamma represents the first identified gene whose expression is lost in the majority of human pituitary tumors.