Effects of downregulated HDAC6 expression on the proliferation of lung cancer cells.

Published

Journal Article

Histone deacetylase 6 (HDAC6) is a multifunctional, cytosolic protein deacetylase that primarily acts on alpha-tubulin. Here we report that stable knockdown of HDAC6 expression causes a decrease in the steady-state level of receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor alpha, in A549 lung cancer cells. The decreased levels of in EGFR in HDAC6-knockdown cells, which correlated with increased acetylation of microtubules, were due to increased turnover of EGFR protein. Despite the decrease in EGFR levels, A549 cells lacking functional HDAC6 appeared to grow normally, probably due to increased expression of extracellular signal-regulated kinases 1 and 2. Indeed, HDAC6-knockdown cells were more sensitive than control cells to the MEK inhibitor U0126. These results suggest that HDAC6 inhibitors combined with inhibitors of growth factor signaling may be useful as cancer therapy.

Full Text

Duke Authors

Cited Authors

  • Kamemura, K; Ito, A; Shimazu, T; Matsuyama, A; Maeda, S; Yao, T-P; Horinouchi, S; Khochbin, S; Yoshida, M

Published Date

  • September 2008

Published In

Volume / Issue

  • 374 / 1

Start / End Page

  • 84 - 89

PubMed ID

  • 18602369

Pubmed Central ID

  • 18602369

Electronic International Standard Serial Number (EISSN)

  • 1090-2104

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2008.06.092

Language

  • eng