Ji H, Liu Y E, Jia T, Wang M, Liu J, Xiao G, Joseph B K, Rosen C, Shi Y E
Human Genome Sciences, Inc., Rockville, Maryland 20850-3338, USA.
Cancer Res. 1997 Feb 15;57(4):759-64.
A high-throughput direct-differential cDNA sequencing approach was employed to identify genes differentially expressed in normal breast as compared with breast cancer. Approximately 6000 expressed sequence tags (ESTs) from cDNA libraries of normal breast and breast carcinoma were selected randomly and subjected to EST-sequencing analysis. The relative expression levels of more than 2000 unique EST groups were quantitatively compared in normal versus cancerous breast. Of many putative differentially expressed genes, a breast cancer-specific gene, BCSGC1, which was expressed in high abundance in a breast cancer cDNA library but scarcely in a normal breast cDNA library, was identified as a putative breast cancer marker. In situ hybridization analysis demonstrated stage-specific BCSG1 expression as follows: BCSG1 was undetectable in normal or benign breast lesions, showed partial expression in ductal carcinoma in situ, but was expressed at an extremely high level in advanced infiltrating breast cancer. The predicted amino acid sequence of BCSG1 gene has a significant sequence homology to the non-amyloid beta protein fragment of the Alzheimer's disease amyloid protein. BCSG1 overexpression may indicate breast cancer malignant progression from benign breast or in situ carcinoma to the highly infiltrating carcinoma.
采用高通量直接差异cDNA测序方法，以鉴定与乳腺癌相比在正常乳腺中差异表达的基因。从正常乳腺和乳腺癌的cDNA文库中随机选择约6000个表达序列标签（EST），并进行EST测序分析。对2000多个独特EST组在正常乳腺与癌性乳腺中的相对表达水平进行了定量比较。在许多推测的差异表达基因中，一个乳腺癌特异性基因BCSGC1被鉴定为一个推测的乳腺癌标志物，该基因在乳腺癌cDNA文库中高丰度表达，但在正常乳腺cDNA文库中几乎不表达。原位杂交分析显示BCSG1的表达具有阶段特异性，如下所示：在正常或良性乳腺病变中未检测到BCSG1，在导管原位癌中呈部分表达，但在晚期浸润性乳腺癌中表达水平极高。BCSG1基因预测的氨基酸序列与阿尔茨海默病淀粉样蛋白的非淀粉样β蛋白片段具有显著的序列同源性。BCSG1的过表达可能表明乳腺癌从良性乳腺或原位癌向高度浸润性癌的恶性进展。
