Shen W F, Detmer K, Mathews C H, Hack F M, Morgan D A, Largman C, Lawrence H J
Veterans Affairs Medical Center, San Francisco, CA 94121.
EMBO J. 1992 Mar;11(3):983-9. doi: 10.1002/j.1460-2075.1992.tb05137.x.
We have previously reported that certain genes of the HOX2 cluster of homeobox genes on human chromosome 17 are specifically expressed in human leukemic cell lines with erythroid potential, suggesting that these genes are involved in hematopoietic differentiation. We now show that the expression of the HOX 2.2 gene decreases during erythropoietin-induced differentiation of the erythroid cell line MB02. In order to study the role of the HOX 2.2 homeobox gene in hematopoiesis, vectors producing sense or antisense transcripts were introduced into K562 and HEL cells, pluripotent lines with erythroid and myeloid features. Overexpression of HOX 2.2 is associated with loss of erythroid features in both lines and an increase in certain myelomonocytic markers in K562 cells. Expression of antisense HOX 2.2 is associated with an increase in erythroid features in HEL cells and a mild decrease in myeloid characteristics in K562 cells. Overexpression of the adjacent HOX 2.1 gene in K562 cells does not produce similar phenotype changes. These data demonstrate that modulation of a specific HOX 2 homeobox gene can change the phenotype of somatic cells and suggest that certain HOX 2 genes play a role in blood cell differentiation.
我们之前报道过，位于人类17号染色体上的同源盒基因HOX2簇的某些基因在具有红系分化潜能的人类白血病细胞系中特异性表达，这表明这些基因参与造血分化过程。我们现在发现，在促红细胞生成素诱导红系细胞系MB02分化的过程中，HOX 2.2基因的表达下降。为了研究HOX 2.2同源盒基因在造血过程中的作用，将产生正义或反义转录本的载体导入K562和HEL细胞，这两种细胞系具有红系和髓系特征，属于多能细胞系。HOX 2.2的过表达与这两种细胞系中红系特征的丧失以及K562细胞中某些髓单核细胞标志物的增加有关。反义HOX 2.2的表达与HEL细胞中红系特征的增加以及K562细胞中髓系特征的轻度下降有关。在K562细胞中过表达相邻的HOX 2.1基因不会产生类似的表型变化。这些数据表明，特定HOX 2同源盒基因的调控可以改变体细胞的表型，并提示某些HOX 2基因在血细胞分化中发挥作用。
