A vasoactive intestinal peptide receptor analog alters the expression of homeobox genes.
A vasoactive intestinal peptide receptor analog alters the expression of homeobox genes.
复制标题
血管活性肠肽受体类似物改变同源盒基因的表达。
DOI：
10.1016/s0024-3205(02)02082-9
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发表时间：
2002
期刊：
影响因子：
6.1
通讯作者：
Gozes,Illana
中科院分区：
文献类型：
--
作者：
Steingart,RuthA;Heldenberg,Eitan;Pinhasov,Albert;Brenneman,DouglasE;Fridkin,Mati;Gozes,Illana
血管活性肠肽（VIP）的亲脂性类似物stearyl-Nle17-neurotensin6-11VIP7-28 （SNH）抑制肺癌生长，此前已有报道。SNH抑制肿瘤生长的机制仍在研究中。本研究检测了SNH对表达VIP受体的结肠癌细胞系HT 29同源盒基因的影响。同源盒基因包含一个特征的DNA序列，编码61个氨基酸的同源结构域，结合特定的DNA基序。HOX基因家族包含一个同源结构域，而POU基因家族包含一个额外的DNA结合同源结构域。SNH孵育HT 29细胞；提取RNA，用与各种HOX或POU基因保守区域匹配的引物进行逆转录聚合酶链反应（RT-PCR）。对SNH处理改变的PCR产物进行测序。鉴定出三个候选snh应答基因，HOX A4、HOX B5和PUO V转录因子I （Oct-3）。特异引物的半定量RT-PCR证实，SNH处理后，HOX A4表达水平升高，Oct-3表达水平降低。因此，HOX A4和Oct-3同源盒基因可能部分介导SNH对癌细胞的活性。
A lipophilic analog of vasoactive intestinal peptide (VIP), stearyl-Nle17-neurotensin6–11VIP7–28(SNH), that inhibited lung cancer growth, has been previously described. The mechanism of SNH inhibition of cancer growth is still being elucidated. The present study examined the effects of SNH on homeobox genes in the colon cancer cell line HT 29 that expresses VIP receptors. Homeobox genes contain a characteristic DNA sequence, coding for a stretch of 61 amino acid homeodomain that binds specific DNA motifs. While the HOX gene family contains a single homeodomain, the POU gene family contains an additional DNA binding homeodomain. HT 29 cells were incubated with SNH; RNA was extracted and subjected to reverse-transcription-polymerase chain reaction (RT-PCR) with primers that matched the conserved area of the various HOX or POU genes. The PCR products that were altered by SNH treatment were sequenced. Three candidate SNH-responsive genes, the HOX A4, the HOX B5 and the PUO V transcription factor I (Oct-3) were identified. Semi-quantitative RT-PCR with specific primers confirmed the increase in HOX A4 and the decrease in Oct-3 expression levels following SNH treatment. Thus, the HOX A4 and the Oct-3 homeobox genes may partially mediate SNH activity on cancer cells.