Da. Kirschmann et al., Down-regulation of HP1(Hs alpha) expression is associated with the metastatic phenotype in breast cancer, CANCER RES, 60(13), 2000, pp. 3359-3363
We previously identified a down regulation in heterochromatin-associated pr
otein 1 (HP1)(Hs alpha) expression in MDA-MB-231 breast carcinoma cells (hi
ghly invasive/metastatic) compared with MCF-7 cells (poorly invasive/nonmet
astatic). In this study, we demonstrate that HP1(Hs alpha), but not HP1(Hs
beta) or HP1(Hs gamma), Is down-regulated at the mRNA and protein levels in
highly invasive/metastatic breast cancer cell lines. In agreement, little
to no nuclear HP1(Hs alpha) staining was observed in these cell lines. In c
ontrast, poorly Invasive/nonmetastatic cell lines showed HP1(Hs alpha) loca
lization to the nucleus and nuclear membrane, Transfection of MDA-MB-231 ce
lls with a green fluorescent protein-HP1(Hs alpha) expression vector decrea
sed their ability to invade a collagen IV/laminin/gelatin matrix compared w
ith green fluorescent protein-transfected controls. Consistent with the cel
l culture studies, immunohistochemical analysis of HP1(Hs alpha) protein lo
calization in distant metastatic tissues from breast cancer patients reveal
ed a decrease in the staining intensity and percentage of cells expressing
HP1(Hs alpha) in seven of nine distant metastatic lesions compared with nor
mal mammary and primary tumors. These results demonstrate a role for HP1(Hs
alpha) In breast cancer invasion and metastasis. Given the role of HP1 in
transcriptional silencing In Drosophila, we propose a model in which HP1(Hs
alpha) normally silences genes involved in breast cancer invasion and meta
stasis.