Open AccessCell density-dependent regulation of p73 in breast cancer cells
Author(s) -
Chaitali Tophkhane,
Shuai Yang,
Zhizhuang Joe Zhao,
Xiaohe Yang
Publication year - 2009
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo_00000461
Subject(s) - downregulation and upregulation , biology , gene isoform , oncogene , cell cycle , cell , cytosol , microbiology and biotechnology , subcellular localization , cancer research , gene , genetics , cytoplasm , enzyme , biochemistry
Molecular regulation of p73, a p53 family member, remains unclear. Here we report that p73 expression is significantly regulated by cell densities. In particular, we found that p73alpha and p73beta are differentially regulated. While p73beta protein levels were inversely correlated with cell densities, p73alpha protein levels behaved oppositely. We further showed that density-dependent changes of p73alpha follow the same patterns as E2F-1 and TAp73 mRNA levels, suggesting transcriptional regulation. Our data also suggest that high levels of p73beta at lower densities may be due to increased protein stability. However, AIP-4/Itch appeared not to be involved in downregulation of p73beta at high densities. Moreover, we also found that subcellular location of p73 isoforms changes with the culture density increases. While high level of p73beta at low density was mainly presented in the nucleus, low levels of this protein at high densities were mainly in the cytosol. Taken together, these findings reveal a novel mechanism that differentially regulates p73 isoforms and underscores the role of cell-cell interaction in p73 regulation, which may advance our understanding of p73 expression and function in human cancers.