Alterations in LMTK2, MSMB and HNF1B gene expression are associated with the development of prostate cancer.
Alterations in LMTK2, MSMB and HNF1B gene expression are associated with the development of prostate cancer.
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DOI：
10.1186/1471-2407-10-315
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发表时间：
2010-06-22
期刊：
影响因子：
3.8
通讯作者：
Crundwell M
中科院分区：
文献类型：
--
作者：
Harries LW;Perry JR;McCullagh P;Crundwell M
全基因组关联研究（GWAS）已经确定了几种与前列腺癌相关的遗传变异。大多数这些变体，像其他GWAS关联信号一样，位于潜在候选基因的非编码区，因此可以在mRNA转录水平上起作用。我们通过实时PCR测量了良性和恶性前列腺中7个前列腺癌候选基因的表达和亚型使用，并将这些因素与癌症状态和GWAS风险变体的基因型相关联。我们确定前列腺癌中LMTK 2转录水平仅为良性组织中的32%（p = 3.2 × 10-7），并且在良性组织（n = 39）和恶性组织（n = 21）中变体rs6465657的基因型对LMTK 2表达的独立影响也是明显的（P = 0.002）。我们还发现，虽然HNF 1 B（C）和MSMB 2构成良性组织中的主要亚型（占总HNF 1 B或MSMB表达的90%和98%），但HNF 1 B（B）和MSMB 1在恶性组织中占主导地位（占总HNF 1 B或MSMB表达的95%和96%; P = 1.7 × 10-7和4 × 10-4），表明亚型使用的重大变化。我们的研究结果表明，从LMTK 2，HNF 1B和MSMB候选基因表达的mRNA转录物的量或性质在前列腺癌中改变，并提供了这些基因在这种疾病中的作用的进一步证据。我们检测到的异构体使用的改变突出了替代mRNA加工和mRNA稳定性调节作为潜在重要疾病机制的潜在重要性。
Genome wide association studies (GWAS) have identified several genetic variants that are associated with prostate cancer. Most of these variants, like other GWAS association signals, are located in non-coding regions of potential candidate genes, and thus could act at the level of the mRNA transcript. We measured the expression and isoform usage of seven prostate cancer candidate genes in benign and malignant prostate by real-time PCR, and correlated these factors with cancer status and genotype at the GWAS risk variants. We determined that levels of LMTK2 transcripts in prostate adenocarcinomas were only 32% of those in benign tissues (p = 3.2 × 10-7), and that an independent effect of genotype at variant rs6465657 on LMTK2 expression in benign (n = 39) and malignant tissues (n = 21) was also evident (P = 0.002). We also identified that whilst HNF1B(C) and MSMB2 comprised the predominant isoforms in benign tissues (90% and 98% of total HNF1B or MSMB expression), HNF1B(B) and MSMB1 were predominant in malignant tissue (95% and 96% of total HNF1B or MSMB expression; P = 1.7 × 10-7 and 4 × 10-4 respectively), indicating major shifts in isoform usage. Our results indicate that the amount or nature of mRNA transcripts expressed from the LMTK2, HNF1B and MSMB candidate genes is altered in prostate cancer, and provides further evidence for a role for these genes in this disorder. The alterations in isoform usage we detect highlights the potential importance of alternative mRNA processing and moderation of mRNA stability as potentially important disease mechanisms.
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雄性BRCA1和BRCA2突变载体中的前列腺癌具有更具侵略性的表型。
影响因子：
8.8
作者：
Mitra, A.;Fisher, C.;Foster, C. S.;Jameson, C.;Barbachanno, Y.;Bartlett, J.;Bancroft, E.;Doherty, R.;Kote-Jarai, Z.;Peock, S.;Easton, D.;Eeles, R.
通讯作者：
Eeles, R.
DOI：
10.1016/j.jsbmb.2009.10.001
发表时间：
2010-01-01
影响因子：
4.1
作者：
Ishii, Hirotaka;Kobayashi, Momoko;Sakuma, Yasuo
通讯作者：
Sakuma, Yasuo
影响因子：
4.8
作者：
Harries, LW;Wickham, CL;Ellard, S
通讯作者：
Ellard, S
影响因子：
30.8
作者：
Eeles, Rosalind A.;Kote-Jarai, Zsofia;Easton, Douglas F.
通讯作者：
Easton, Douglas F.
影响因子：
3.5
作者：
Rebouissou, S;Vasiliu, V;Zucman-Rossi, J
通讯作者：
Zucman-Rossi, J