Characterization of frequently deleted 6q locus in prostate cancer.

Characterization of frequently deleted 6q locus in prostate cancer.
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前列腺癌中频繁缺失的 6q 位点的表征。

DOI:
10.1089/dna.2006.25.597
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发表时间:
2006
影响因子:
3.1
通讯作者:
Srivastava,Shiv
Srivastava,Shiv
中科院分区:
生物学4区
文献类型:
--
作者:
Sun,Mei;Srikantan,Vasantha;Ma,Lanfeng;Li,Jia;Zhang,Wei;Petrovics,Gyorgy;Makarem,Mazen;Strovel,JeffreyW;Horrigan,StephenG;Augustus,Meena;Sesterhenn,IsabellA;Moul,JuddW;Chandrasekharappa,Settara;Zou,Zhiqiang;Srivastava,Shiv

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6号染色体长臂在多种人类肿瘤中经常缺失。我们以前的研究表明,在原发性前列腺癌(CaP)的染色体6 q上的标记D 6S 1056和D 6S 300之间的最小缺失区域。在这项研究中,我们进一步完善了一个200 kb的最小区域的缺失(6 qTSG 1)为中心的D 6S 1013标记。6 qTSG 1转录物含有复杂的多个剪接变体,在CaP细胞中表达较低或不表达。在NCBI数据库中,所鉴定的转录本均不包含编码蛋白质的开放阅读框。6 qTSG转录本的表达揭示了与CaP生物学相关的有趣的激素调节。在活性炭去除血清培养基中培养的LNCaP细胞中诱导了6 qTSG转录本的表达,表明雄激素去除和细胞生长抑制/凋亡上调了6 qTSG转录本。在雄激素非依赖性衍生的LNCaP细胞中,对雄激素去除的6 qTSG 1表达诱导被废除。总之,我们在染色体6q16.1上确定了一个候选的CaP抑制基因位点,该位点的缺失通常与前列腺肿瘤发生相关。鉴于非编码RNA在包括CaP在内的癌症生物学中的新作用,6 qTSG 11位点的未来研究是必要的。
The long arm of chromosome 6 is frequently deleted in diverse human neoplasms. Our previous study showed a minimum deletion region between markers D6S1056 and D6S300 on chromosome 6q in primary prostate cancer (CaP). In this study, we further refined a 200-kb minimal region of deletion (6qTSG1) centered around D6S1013 marker. The 6qTSG1 transcripts contained complex multiple splicing variants with low or absent expression in CaP cells. None of the transcripts identified contained open reading frames that code for a protein in the NCBI database. The expression of6qTSGtranscripts revealed interesting hormonal regulation relevant to CaP biology. Expression of 6q TSG transcript was induced in LNCaP cells that were cultured in charcoal-stripped serum medium suggesting an upregulation of 6qTSG transcript by androgen ablation and cell growth inhibition/apoptosis. Induction of 6qTSG1 expression in response to androgen ablation was abrogated in androgen-independent derivatives of LNCaP cells. In summary, we have defined a candidate CaP suppressor locus on chromosome 6q16.1, and deletions of this locus are frequently associated with prostate tumorigenesis. In the light of emerging role of noncoding RNAs in cancer biology including CaP, future investigations of 6qTSG11 locus is warranted.