Downregulation of the RUNX3 gene by promoter hypermethylation and hemizygous deletion in breast cancer.
Downregulation of the RUNX3 gene by promoter hypermethylation and hemizygous deletion in breast cancer.
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DOI：
10.3346/jkms.2007.22.s.s24
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发表时间：
2007-09
影响因子：
4.5
通讯作者：
Noh DY
中科院分区：
文献类型：
--
作者：
Hwang KT;Han W;Bae JY;Hwang SE;Shin HJ;Lee JE;Kim SW;Min HJ;Noh DY
RUNX 3基因被认为是许多人类实体瘤中的抑癌基因，其失活被认为与实体瘤的发生有关。由于有关RUNX 3基因在乳腺癌中的作用的信息很少，我们研究了RUNX 3基因与乳腺癌之间的关系。我们进行了逆转录-聚合酶链反应（RT-PCR），甲基化特异性PCR和双色荧光原位杂交分析，试图揭示相关的机制。本研究中使用了40个乳腺组织样本和13个细胞系。85%的乳腺癌组织显示RUNX 3基因表达下调，而通过RT-PCR检测，RUNX 3基因在正常乳腺组织中仅下调25%。67%的乳腺癌细胞系显示RUNX 3表达下调，但RUNX 3基因在两个正常乳腺细胞系中不表达。在53%的乳腺癌组织和57%的乳腺癌细胞系中观察到超甲基化。在43%的乳腺癌细胞系中观察到半合子缺失。在7个乳腺癌细胞系中的5个中观察到高甲基化和/或半合子缺失，并且这5个细胞系中的4个未显示RUNX 3基因表达。我们认为，多种机制，包括甲基化和半合子缺失，可能有助于RUNX 3基因失活。
The RUNX3 gene is regarded as a tumor suppressor gene in many human solid tumors, and its inactivation is believed to be related with solid tumor carcinogenesis. As little information is available about the role of the RUNX3 gene in breast cancer, we investigated the relationship between the RUNX3 gene and breast cancer. We performed reverse transcriptase-polymerases chain reaction (RT-PCR), methylation specific PCR, and bicolor fluorescent in situ hybridization analysis in an effort to reveal related mechanisms. Forty breast tissue samples and 13 cell lines were used in this study. Eighty-five percent of breast cancer tissues showed downregulated RUNX3 gene expression, whereas it was downregulated in only 25% of normal breast tissues by RT-PCR assay. Sixty-seven percent of breast cancer cell lines showed downregulated RUNX3 expression, but the RUNX3 gene was not expressed in two normal breast cell lines. Hypermethylation was observed in 53% of breast cancer tissues and 57% of breast cancer cell lines. Hemizygous deletion was observed in 43% of breast cancer cell lines. Hypermethylation and/or hemizygous deletion was observed in 5 of 7 breast cancer cell lines, and the four of these five examined showed no RUNX3 gene expression. We suggest that various mechanisms, including methylation and hemizygous deletion, could contribute to RUNX3 gene inactivation.