Androgen control of cell proliferation and cytoskeletal reorganization in human fibrosarcoma cells: Role of RhoB signaling

Sanjay Chauhan, Susan Kunz, Kelli Davis, Jordan Roberts, Greg Martin, Manolis C. Demetriou, Thomas C. Sroka, Anne E Cress, Roger Miesfeld

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We recently generated an HT-1080-derived cell line called HT-AR1 that responds to dihydrotestosterone (DHT) treatment by undergoing cell growth arrest in association with cytoskeletal reorganization and induction of neuroendocrine-like cell differentiation. In this report, we show that DHT induces a dose-dependent increase in G0/G1 growth-arrested cells using physiological levels of hormone. The arrested cells increase in cell size and contain a dramatic redistribution of desmoplakin, keratin 5, and chromogranin A proteins. DHT-induced cytoskeletal changes were also apparent from time lapse video microscopy that showed that androgen treatment resulted in the rapid appearance of neuronal-like membrane extensions. Expression profiling analysis using RNA isolated from DHT-treated HT-AR1 cells revealed that androgen receptor activation leads to the coordinate expression of numerous cell signaling genes including RhoB, PTGF-β, caveolin-2, Egr-1, myosin 1B, and EHM2. Because RhoB has been shown to have a role in tumor suppression and neuronal differentiation in other cell types, we investigated RhoB signaling functions in the HT-AR1 steroid response. We found that steroid induction of RhoB was DHT-specific and that newly synthesized RhoB protein was post-translationally modified and localized to endocytic vesicles. Moreover, treatment with a farnesyl transferase inhibitor reduced DHT-dependent growth arrest, suggesting that prenylated RhoB might function to inhibit HT-AR1 cell proliferation. This was directly shown by transfecting HT-AR1 cells with RhoB coding sequences containing activating or dominant negative mutations.

Original languageEnglish (US)
Pages (from-to)937-944
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number2
DOIs
StatePublished - Jan 9 2004

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Dihydrotestosterone
Fibrosarcoma
Cell proliferation
Androgens
Cell Proliferation
Cell growth
rhoB GTP-Binding Protein
Caveolin 2
Desmoplakins
Steroids
Cells
Keratin-5
Cell signaling
Growth
Chromogranin A
Androgen Receptors
Video Microscopy
Transport Vesicles
Neuroendocrine Cells
Myosins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Androgen control of cell proliferation and cytoskeletal reorganization in human fibrosarcoma cells : Role of RhoB signaling. / Chauhan, Sanjay; Kunz, Susan; Davis, Kelli; Roberts, Jordan; Martin, Greg; Demetriou, Manolis C.; Sroka, Thomas C.; Cress, Anne E; Miesfeld, Roger.

In: Journal of Biological Chemistry, Vol. 279, No. 2, 09.01.2004, p. 937-944.

Research output: Contribution to journalArticle

Chauhan, Sanjay ; Kunz, Susan ; Davis, Kelli ; Roberts, Jordan ; Martin, Greg ; Demetriou, Manolis C. ; Sroka, Thomas C. ; Cress, Anne E ; Miesfeld, Roger. / Androgen control of cell proliferation and cytoskeletal reorganization in human fibrosarcoma cells : Role of RhoB signaling. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 2. pp. 937-944.
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