Heregulin is rapidly translocated to the nucleus and its transport is correlated with c-myc induction in breast cancer cells.
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.
Li
W
W
Genentech, Inc., South San Francisco, California 94080, USA.
Park
J W
JW
Nuijens
A
A
Sliwkowski
M X
MX
Keller
G A
GA
D001943:Breast Neoplasms / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009363:Neoplasm Proteins / Q000378:metabolism*; D020890:Neuregulin-1; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020893:Receptor, ErbB-3; D015854:Up-Regulation
D002352:Carrier Proteins; D066246:ErbB Receptors; D006023:Glycoproteins; D009363:Neoplasm Proteins; D020890:Neuregulin-1; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C087230:heregulin beta1