Effect of the hsp90 inhibitor geldanamycin on androgen response of prostate cancer under hypoxic conditions

Yasutomo Suzuki, Yukihiro Kondo, Shuntaro Hara, Ryouji Kimata, Taiji Nishimura
International Journal of Urology: Official Journal of the Japanese Urological Association 2010, 17 (3): 281-5

OBJECTIVES: To investigate the androgen response of hormone-dependent prostate cancer cells under hypoxia and to examine the effect of geldanamycin (GA), a heat shock protein 90 (Hsp90)-specific inhibitor, on the androgen response.

METHODS: LNCaP cells were cultured with or without GA under normoxic or hypoxic conditions. Cell viability was examined in response to dihydrotestosterone (DHT). Luciferase reporter gene assay was used to measure androgen response element (ARE)- and hypoxia response element (HRE)-mediated transcriptional activities. Western blot was used to analyze the protein levels of androgen receptor (AR), hypoxia-inducible factor-1alpha (HIF-1alpha) and Hsp90.

RESULTS: The DHT-dependent growth and ARE-mediated transcriptional activities of LNCaP cells were depressed under hypoxic conditions. However, these effects were recovered after incubation with GA. In contrast, hypoxia-induced HRE-mediated transcriptional activity, which was dose-dependently increased by DHT, was suppressed by GA. The expression of AR, HIF-1alpha and Hsp90 proteins were decreased under hypoxic conditions by adding GA.

CONCLUSIONS: Geldanamycin increases the androgen response regardless of AR protein in hormone-dependent prostate cancer cells under hypoxic conditions.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"