Farnesyltransferase and geranylgeranyltransferase I inhibitors upregulate RhoB expression by HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter

F. L. Delarue, J. Adnane, B. Joshi, M. A. Blaskovich, D. A. Wang, J. Hawker, F. Bizouarn, J. Ohkanda, K. Zhu, Andrew Hamilton, S. Chellappan, S. M. Sebti

Research output: Contribution to journalArticle

Abstract

Recently, we have shown that RhoB suppresses EGFR-, ErbB2-, Ras- and Akt-mediated malignant transformation and metastasis. In this paper, we demonstrate that the novel antitumor agents farnesyltransferase inhibitors (FTIs) and geranylgeranyltransferase I inhibitors (GGTIs) upregulate RhoB expression in a wide spectrum of human cancer cells including those from pancreatic, breast, lung, colon, bladder and brain cancers. RhoB induction by FTI-277 and GGTI-298 occurs at the transcriptional level and is blocked by actinomycin D. Reverse transcription-PCR experiments documented that the increase in RhoB protein levels is due to an increase in RhoB transcription. Furthermore, treatment with FTIs and GGTIs of cancer cells results in HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter. Thus, promoter acetylation is a novel mechanism by which RhoB expression levels are regulated following treatment with the anticancer agents FTIs and GGTIs.

Original languageEnglish (US)
Pages (from-to)633-640
Number of pages8
JournalOncogene
Volume26
Issue number5
DOIs
StatePublished - Feb 1 2007

Fingerprint

Farnesyltranstransferase
Acetylation
Histones
Up-Regulation
Antineoplastic Agents
rhoB GTP-Binding Protein
Dactinomycin
Pancreatic Neoplasms
Urinary Bladder Neoplasms
Brain Neoplasms
Colonic Neoplasms
Reverse Transcription
Lung Neoplasms
Neoplasms
Breast Neoplasms
Neoplasm Metastasis
Polymerase Chain Reaction
geranylgeranyltransferase type-I

Keywords

  • Farnesyltransferase inhibitors
  • Geranylgeranyltransferase inhibitors
  • HAT association
  • HDAC1 dissociation
  • Histone acetylation
  • RhoB

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Farnesyltransferase and geranylgeranyltransferase I inhibitors upregulate RhoB expression by HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter. / Delarue, F. L.; Adnane, J.; Joshi, B.; Blaskovich, M. A.; Wang, D. A.; Hawker, J.; Bizouarn, F.; Ohkanda, J.; Zhu, K.; Hamilton, Andrew; Chellappan, S.; Sebti, S. M.

In: Oncogene, Vol. 26, No. 5, 01.02.2007, p. 633-640.

Research output: Contribution to journalArticle

Delarue, FL, Adnane, J, Joshi, B, Blaskovich, MA, Wang, DA, Hawker, J, Bizouarn, F, Ohkanda, J, Zhu, K, Hamilton, A, Chellappan, S & Sebti, SM 2007, 'Farnesyltransferase and geranylgeranyltransferase I inhibitors upregulate RhoB expression by HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter', Oncogene, vol. 26, no. 5, pp. 633-640. https://doi.org/10.1038/sj.onc.1209819
Delarue, F. L. ; Adnane, J. ; Joshi, B. ; Blaskovich, M. A. ; Wang, D. A. ; Hawker, J. ; Bizouarn, F. ; Ohkanda, J. ; Zhu, K. ; Hamilton, Andrew ; Chellappan, S. ; Sebti, S. M. / Farnesyltransferase and geranylgeranyltransferase I inhibitors upregulate RhoB expression by HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter. In: Oncogene. 2007 ; Vol. 26, No. 5. pp. 633-640.
@article{873f903c77584760b786a17d775a0601,
title = "Farnesyltransferase and geranylgeranyltransferase I inhibitors upregulate RhoB expression by HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter",
abstract = "Recently, we have shown that RhoB suppresses EGFR-, ErbB2-, Ras- and Akt-mediated malignant transformation and metastasis. In this paper, we demonstrate that the novel antitumor agents farnesyltransferase inhibitors (FTIs) and geranylgeranyltransferase I inhibitors (GGTIs) upregulate RhoB expression in a wide spectrum of human cancer cells including those from pancreatic, breast, lung, colon, bladder and brain cancers. RhoB induction by FTI-277 and GGTI-298 occurs at the transcriptional level and is blocked by actinomycin D. Reverse transcription-PCR experiments documented that the increase in RhoB protein levels is due to an increase in RhoB transcription. Furthermore, treatment with FTIs and GGTIs of cancer cells results in HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter. Thus, promoter acetylation is a novel mechanism by which RhoB expression levels are regulated following treatment with the anticancer agents FTIs and GGTIs.",
keywords = "Farnesyltransferase inhibitors, Geranylgeranyltransferase inhibitors, HAT association, HDAC1 dissociation, Histone acetylation, RhoB",
author = "Delarue, {F. L.} and J. Adnane and B. Joshi and Blaskovich, {M. A.} and Wang, {D. A.} and J. Hawker and F. Bizouarn and J. Ohkanda and K. Zhu and Andrew Hamilton and S. Chellappan and Sebti, {S. M.}",
year = "2007",
month = "2",
day = "1",
doi = "10.1038/sj.onc.1209819",
language = "English (US)",
volume = "26",
pages = "633--640",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Farnesyltransferase and geranylgeranyltransferase I inhibitors upregulate RhoB expression by HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter

AU - Delarue, F. L.

AU - Adnane, J.

AU - Joshi, B.

AU - Blaskovich, M. A.

AU - Wang, D. A.

AU - Hawker, J.

AU - Bizouarn, F.

AU - Ohkanda, J.

AU - Zhu, K.

AU - Hamilton, Andrew

AU - Chellappan, S.

AU - Sebti, S. M.

PY - 2007/2/1

Y1 - 2007/2/1

N2 - Recently, we have shown that RhoB suppresses EGFR-, ErbB2-, Ras- and Akt-mediated malignant transformation and metastasis. In this paper, we demonstrate that the novel antitumor agents farnesyltransferase inhibitors (FTIs) and geranylgeranyltransferase I inhibitors (GGTIs) upregulate RhoB expression in a wide spectrum of human cancer cells including those from pancreatic, breast, lung, colon, bladder and brain cancers. RhoB induction by FTI-277 and GGTI-298 occurs at the transcriptional level and is blocked by actinomycin D. Reverse transcription-PCR experiments documented that the increase in RhoB protein levels is due to an increase in RhoB transcription. Furthermore, treatment with FTIs and GGTIs of cancer cells results in HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter. Thus, promoter acetylation is a novel mechanism by which RhoB expression levels are regulated following treatment with the anticancer agents FTIs and GGTIs.

AB - Recently, we have shown that RhoB suppresses EGFR-, ErbB2-, Ras- and Akt-mediated malignant transformation and metastasis. In this paper, we demonstrate that the novel antitumor agents farnesyltransferase inhibitors (FTIs) and geranylgeranyltransferase I inhibitors (GGTIs) upregulate RhoB expression in a wide spectrum of human cancer cells including those from pancreatic, breast, lung, colon, bladder and brain cancers. RhoB induction by FTI-277 and GGTI-298 occurs at the transcriptional level and is blocked by actinomycin D. Reverse transcription-PCR experiments documented that the increase in RhoB protein levels is due to an increase in RhoB transcription. Furthermore, treatment with FTIs and GGTIs of cancer cells results in HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter. Thus, promoter acetylation is a novel mechanism by which RhoB expression levels are regulated following treatment with the anticancer agents FTIs and GGTIs.

KW - Farnesyltransferase inhibitors

KW - Geranylgeranyltransferase inhibitors

KW - HAT association

KW - HDAC1 dissociation

KW - Histone acetylation

KW - RhoB

UR - http://www.scopus.com/inward/record.url?scp=33846813827&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846813827&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1209819

DO - 10.1038/sj.onc.1209819

M3 - Article

VL - 26

SP - 633

EP - 640

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 5

ER -