Li W, Park J W, Nuijens A, Sliwkowski M X, Keller G A
Genentech, Inc., South San Francisco, California 94080, USA.
Oncogene. 1996 Jun 6;12(11):2473-7.
Heregulins (neuregulins) are a family of proteins known to interact and activate the receptor tyrosine kinases ErbB2 in association with ErbB3 or ErbB4. Using immunofluorescence microscopy, electron microscopy autoradiography, and SDS-PAGE analysis of nuclear fractions, we show that the heregulin-beta1(1-244) isoform is rapidly internalized and translocated to the nucleus of SK-BR-3 breast cancer cells as an intact molecule. Heregulin-beta 1(1-244) treatment up-regulated expression of c-myc mRNA and protein, which was also observed to undergo its own translocation from the cytosol to the nucleus. c-myc thus appears to be a cellular target gene of HRGbeta 1(1-244), and its induction may be related to the nuclear translocation of heregulin.
这里调节素（神经调节素）是一类已知能与ErbB3或ErbB4相互作用并激活受体酪氨酸激酶ErbB2的蛋白质家族。利用免疫荧光显微镜、电子显微镜放射自显影以及细胞核组分的SDS-PAGE分析，我们发现这里调节素-β1(1-244)亚型作为完整分子迅速内化并转运至SK-BR-3乳腺癌细胞的细胞核。这里调节素-β1(1-244)处理上调了c-myc mRNA和蛋白质的表达，同时也观察到c-myc自身从细胞质转运至细胞核。因此，c-myc似乎是HRGβ1(1-244)的细胞靶基因，其诱导可能与这里调节素的核转运有关。
