Mutation and expression analysis of the putative prostate tumour-suppressor gene PTEN.

Mutation and expression analysis of the putative prostate tumour-suppressor gene PTEN.
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DOI:
10.1038/bjc.1998.674
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发表时间:
1998-11
影响因子:
8.8
通讯作者:
Snary, D
Snary, D
中科院分区:
医学1区
文献类型:
--
作者:
Gray, IC;Stewart, LMD;Phillips, SMA;Hamilton, JA;Gray, NE;Watson, GJ;Spurr, NK;Snary, D

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染色体区域10 q23 -24在许多肿瘤类型中经常缺失,包括前列腺腺癌和神经胶质瘤。一个位于10q23.3的候选肿瘤抑制基因,命名为PTEN或MMAC 1,具有假定的肌动蛋白结合和酪氨酸磷酸酶结构域。已在源自神经胶质瘤、黑素瘤和前列腺肿瘤的细胞系中以及源自神经胶质、乳腺、子宫内膜和肾组织的许多肿瘤标本中鉴定了PTEN突变。PTEN的生殖系突变似乎是导致Cowden病的原因。我们在分析的37例原发性前列腺肿瘤中发现了5个PTEN突变,发现70%的肿瘤显示至少一个PTEN等位基因的丢失或改变,支持PTEN参与前列腺肿瘤进展的证据。我们提出了抗血清从PTEN的肽,并表明反应发生在许多小的细胞质细胞器和蛋白质通常在各种细胞类型中表达。北方印迹分析揭示了多种RNA种类;一些是由于选择性多聚腺苷酸化位点而产生的,但其他的可能是由于选择性剪接。
The chromosomal region 10q23-24 is frequently deleted in a number of tumour types, including prostate adenocarcinoma and glioma. A candidate tumour-suppressor gene at 10q23.3, designated PTENor MMAC1, with putative actin-binding and tyrosine phosphatase domains has recently been described. Mutations in PTEN have been identified in cell lines derived from gliomas, melanomas and prostate tumours and from a number of tumour specimens derived from glial, breast, endometrial and kidney tissue. Germline mutations in PTEN appear to be responsible for Cowden disease. We identified five PTEN mutations in 37 primary prostatic tumours analysed and found that 70% of tumours showed loss or alteration of at least one PTEN allele, supporting the evidence for PTEN involvement in prostate tumour progression. We raised antisera to a peptide from PTEN and showed that reactivity occurs in numerous small cytoplasmic organelles and that the protein is commonly expressed in a variety of cell types. Northern blot analysis revealed multiple RNA species; some arise as a result of alternative polyadenylation sites, but others may be due to alternative splicing.
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