Differentiation of human hepatoma cells during confluence as revealed by gene expression profiling
- 作者：Butura ; Angelica ; Johansson ; Inger ; Nilsson ; Kerstin ; Wä ; rngå ; rd ; Lars ; Ingelman-Sundberg ; Magnus ; et. al.
- 关键词：CYP ; cytochrome P450 ; HL ; human liver ; PC ; principal component ; PCA ; principal component analysis ; LETF ; liver-enriched transcription factor ; Microarray ; Liver-enriched transcription factor ; Cytochrome P450 ; Wnt signaling ; PCA analysis ; Cluster analysis
- 刊名：Biochemical Pharmacology
- 出版年：2004
- 期刊代码：2_00062952
- 类别：pha
- 出版时间：April 1, 2004
- 卷：67
- 期：7
- 页码：1249-1258
- 文件大小：533 K
摘要
Certain human hepatocarcinoma cells undergo differentiation when grown at confluence. In order to understand the basis for this differentiation, we investigated the phenotypic changes occurring during confluent growth of the human hepatoma B16A2 cell line. The global gene expression profile of B16A2 cells grown during confluence for 5 weeks was investigated using microarrays containing complementary sequences corresponding to approximately 10,000 genes, and compared with profiles of adult human liver and HepG2 cells. The major part of gene products detected were shared by all three systems and the hepatoma cell lines expressed surprisingly high levels of liver-enriched transcription factors. During confluence of B16A2 cells, the majority of transcriptional changes monitored were directed towards the phenotype of adult human liver in vivo, although the changes accounted for less than 10%of those necessary to acquire a native hepatic phenotype. Several markers of liver differentiation and regeneration were changed in similar manner as observed in developing liver and during liver regeneration. In conclusion, the data indicate that differentiation in vitro of the B16A2 cell line during confluence partially resembles that of hepatic differentiation and regeneration in vivo, implying a partial normalization of a low differentiated phenotype.