Skip to content

Research at St Andrews

The role of HDAC2 in chromatin remodelling and response to chemotherapy in ovarian cancer

Research output: Contribution to journalArticle

Standard

The role of HDAC2 in chromatin remodelling and response to chemotherapy in ovarian cancer. / Huang, Rui; Langdon, Simon P.; Tse, Matthew; Mullen, Peter; Um, In Hwa; Faratian, Dana; Harrison, David James.

In: Oncotarget, Vol. 7, No. 4, 14.12.2015, p. 4695-4711.

Research output: Contribution to journalArticle

Harvard

Huang, R, Langdon, SP, Tse, M, Mullen, P, Um, IH, Faratian, D & Harrison, DJ 2015, 'The role of HDAC2 in chromatin remodelling and response to chemotherapy in ovarian cancer' Oncotarget, vol. 7, no. 4, pp. 4695-4711. https://doi.org/10.18632/oncotarget.6618

APA

Huang, R., Langdon, S. P., Tse, M., Mullen, P., Um, I. H., Faratian, D., & Harrison, D. J. (2015). The role of HDAC2 in chromatin remodelling and response to chemotherapy in ovarian cancer. Oncotarget, 7(4), 4695-4711. https://doi.org/10.18632/oncotarget.6618

Vancouver

Huang R, Langdon SP, Tse M, Mullen P, Um IH, Faratian D et al. The role of HDAC2 in chromatin remodelling and response to chemotherapy in ovarian cancer. Oncotarget. 2015 Dec 14;7(4):4695-4711. https://doi.org/10.18632/oncotarget.6618

Author

Huang, Rui ; Langdon, Simon P. ; Tse, Matthew ; Mullen, Peter ; Um, In Hwa ; Faratian, Dana ; Harrison, David James. / The role of HDAC2 in chromatin remodelling and response to chemotherapy in ovarian cancer. In: Oncotarget. 2015 ; Vol. 7, No. 4. pp. 4695-4711.

Bibtex - Download

@article{6f3631466be0430ba0143f5e7d8144b5,
title = "The role of HDAC2 in chromatin remodelling and response to chemotherapy in ovarian cancer",
abstract = "Chromatin undergoes structural changes in response to extracellular and environmental signals. We observed changes in nuclear morphology in cancer tissue biopsied after chemotherapy and hypothesised that these DNA damage-induced changes are mediated by histone deacetylases (HDACs). Nuclear morphological changes in cell lines and a xenograft model (OV1002) weremeasured in response to platinum chemotherapy by image analysis of nuclear texture. HDAC2 expression increased in PEO1 cells treated with cisplatin at 24h, which was accompanied by increased expression of heterochromatin protein 1 (HP1). HDAC2 and HP1 expression were also increased after carboplatin treatment in the OV1002 carboplatin-sensitive xenograft model but notin the insensitive HOX424 model. Expression of DNA damage response pathways (pBRCA1, γH2AX, pATM, pATR) showed time-dependent changes after cisplatin treatment. HDAC2 knockdown by siRNA reduced HP1 expression, induced DNA double strand breaks (DSB) measured by γH2AX, and interfered with the activation of DNA damage responses induced by cisplatin. Furthermore, HDAC2depletion affected γH2AX foci formation, cell cycle distribution, and apoptosis triggered by cisplatin and was additive to the inhibitory effect of cisplatin in cell lines. By inhibiting HDAC2 expression, reversible alterations in chromatin patterns during cisplatin treatment were observed. These results demonstrate quantifiable alterations in nuclear morphology after chemotherapy and implicateHDAC2 in higher-order chromatin changes and cellular DNA damage responses in ovarian cancer cells in vitro and in vivo.",
keywords = "HDAC2, Chromatin, Platinum, Ovarian cancer, DNA repair, Chemotherapy",
author = "Rui Huang and Langdon, {Simon P.} and Matthew Tse and Peter Mullen and Um, {In Hwa} and Dana Faratian and Harrison, {David James}",
note = "This study was supported by financial support from the University of Edinburgh/China Scholarship Council joint Scholarship Scheme. We are also grateful to support from the Scottish Funding Council.",
year = "2015",
month = "12",
day = "14",
doi = "10.18632/oncotarget.6618",
language = "English",
volume = "7",
pages = "4695--4711",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "4",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - The role of HDAC2 in chromatin remodelling and response to chemotherapy in ovarian cancer

AU - Huang, Rui

AU - Langdon, Simon P.

AU - Tse, Matthew

AU - Mullen, Peter

AU - Um, In Hwa

AU - Faratian, Dana

AU - Harrison, David James

N1 - This study was supported by financial support from the University of Edinburgh/China Scholarship Council joint Scholarship Scheme. We are also grateful to support from the Scottish Funding Council.

PY - 2015/12/14

Y1 - 2015/12/14

N2 - Chromatin undergoes structural changes in response to extracellular and environmental signals. We observed changes in nuclear morphology in cancer tissue biopsied after chemotherapy and hypothesised that these DNA damage-induced changes are mediated by histone deacetylases (HDACs). Nuclear morphological changes in cell lines and a xenograft model (OV1002) weremeasured in response to platinum chemotherapy by image analysis of nuclear texture. HDAC2 expression increased in PEO1 cells treated with cisplatin at 24h, which was accompanied by increased expression of heterochromatin protein 1 (HP1). HDAC2 and HP1 expression were also increased after carboplatin treatment in the OV1002 carboplatin-sensitive xenograft model but notin the insensitive HOX424 model. Expression of DNA damage response pathways (pBRCA1, γH2AX, pATM, pATR) showed time-dependent changes after cisplatin treatment. HDAC2 knockdown by siRNA reduced HP1 expression, induced DNA double strand breaks (DSB) measured by γH2AX, and interfered with the activation of DNA damage responses induced by cisplatin. Furthermore, HDAC2depletion affected γH2AX foci formation, cell cycle distribution, and apoptosis triggered by cisplatin and was additive to the inhibitory effect of cisplatin in cell lines. By inhibiting HDAC2 expression, reversible alterations in chromatin patterns during cisplatin treatment were observed. These results demonstrate quantifiable alterations in nuclear morphology after chemotherapy and implicateHDAC2 in higher-order chromatin changes and cellular DNA damage responses in ovarian cancer cells in vitro and in vivo.

AB - Chromatin undergoes structural changes in response to extracellular and environmental signals. We observed changes in nuclear morphology in cancer tissue biopsied after chemotherapy and hypothesised that these DNA damage-induced changes are mediated by histone deacetylases (HDACs). Nuclear morphological changes in cell lines and a xenograft model (OV1002) weremeasured in response to platinum chemotherapy by image analysis of nuclear texture. HDAC2 expression increased in PEO1 cells treated with cisplatin at 24h, which was accompanied by increased expression of heterochromatin protein 1 (HP1). HDAC2 and HP1 expression were also increased after carboplatin treatment in the OV1002 carboplatin-sensitive xenograft model but notin the insensitive HOX424 model. Expression of DNA damage response pathways (pBRCA1, γH2AX, pATM, pATR) showed time-dependent changes after cisplatin treatment. HDAC2 knockdown by siRNA reduced HP1 expression, induced DNA double strand breaks (DSB) measured by γH2AX, and interfered with the activation of DNA damage responses induced by cisplatin. Furthermore, HDAC2depletion affected γH2AX foci formation, cell cycle distribution, and apoptosis triggered by cisplatin and was additive to the inhibitory effect of cisplatin in cell lines. By inhibiting HDAC2 expression, reversible alterations in chromatin patterns during cisplatin treatment were observed. These results demonstrate quantifiable alterations in nuclear morphology after chemotherapy and implicateHDAC2 in higher-order chromatin changes and cellular DNA damage responses in ovarian cancer cells in vitro and in vivo.

KW - HDAC2

KW - Chromatin

KW - Platinum

KW - Ovarian cancer

KW - DNA repair

KW - Chemotherapy

U2 - 10.18632/oncotarget.6618

DO - 10.18632/oncotarget.6618

M3 - Article

VL - 7

SP - 4695

EP - 4711

JO - Oncotarget

T2 - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 4

ER -

Related by author

  1. Genome-scale CRISPR/Cas9 screen determines factors modulating sensitivity to ProTide NUC-1031

    Sarr, A., Bré, J., Um, I. H., Chan, T. H., Mullen, P., Harrison, D. J. & Reynolds, P. A., 21 May 2019, In : Scientific Reports. 9, 13 p., 7643.

    Research output: Contribution to journalArticle

  2. Evaluation of carbonic anhydrase IX as a therapeutic target for inhibition of breast cancer invasion and metastasis using a series of in vitro breast cancer models

    Ward, C., Meehan, J., Mullen, P., Supuran, C., Dixon, J. M., Thomas, J. S., Winum, J-Y., Lambin, P., Dubois, L., Pavathaneni, N-K., Jarman, E. J., Renshaw, L., Um, I. H., Kay, C., Harrison, D. J., Kunkler, I. H. & Langdon, S. P., 2015, In : Oncotarget. 6, 28, p. 24865-24870 15 p.

    Research output: Contribution to journalArticle

  3. Characterisation of phosphorylated checkpoint kinase 1 as a poor prognostic biomarker in serous ovarian cancer

    Francis, K. E., Mullen, P., Um, I., Kay, C., Harrison, D. J. & Langdon, S. P., Sep 2013, In : Journal of Pathology. 231, p. 46 1 p.

    Research output: Contribution to journalAbstract

  4. Overcoming intratumoural heterogeneity for reproducible molecular risk stratification: a case study in advanced kidney cancer

    Lubbock, A. L. R., Stewart, G. D., O'Mahoney, F. C., Laird, A., Mullen, P., O'Donnell, M., Powles, T., Harrison, D. J. & Overton, I. M., 26 Jun 2017, In : BMC Medicine. 15, 12 p., 118.

    Research output: Contribution to journalArticle

  5. A signaling visualization toolkit to support rational design of combination therapies and biomarker discovery: SiViT

    Brown, J. L., Shovman, M., Robertson, P., Boiko, A., Goltsov, A., Mullen, P. & Harrison, D. J., May 2017, In : Oncotarget. 8, 18, p. 29657-29667 11 p.

    Research output: Contribution to journalArticle

Related by journal

  1. A signaling visualization toolkit to support rational design of combination therapies and biomarker discovery: SiViT

    Brown, J. L., Shovman, M., Robertson, P., Boiko, A., Goltsov, A., Mullen, P. & Harrison, D. J., May 2017, In : Oncotarget. 8, 18, p. 29657-29667 11 p.

    Research output: Contribution to journalArticle

  2. Inhibition of pH regulation as a therapeutic strategy in hypoxic human breast cancer cells

    Meehan, J., Ward, C., Turnbull, A., Bukowski-Wills, J., Finch, A., Jarman, E. J., Xintaropoulou, C., Martinez-Perez, C., Gray, M., Pearson, M., Mullen, P., Supuran, C. T., Carta, F., Harrison, D. J., Kunkler, I. H. & Langdon, S., 2017, In : Oncotarget. 8, 26, p. 42857-42875

    Research output: Contribution to journalArticle

  3. A novel mechanism of action of HER2 targeted immunotherapy is explained by inhibition of NRF2 function in ovarian cancer cells

    Khalil, H. S., Langdon, S. P., Goltsov, A., Soininen, T., Harrison, D. J., Brown, J. & Deeni, Y. Y., 2016, In : Oncotarget. 7, 46, p. 75874-75901

    Research output: Contribution to journalArticle

  4. Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis

    Zeissler, M-L., Eastwood, J., McCorry, K., Hanemann, C. O., Zajicek, J. P. & Carroll, C. B., 27 Jun 2016, In : Oncotarget. 7, 29, p. 46603-46614 12 p.

    Research output: Contribution to journalArticle

  5. Dynamic epigenetic changes to VHL occur with sunitinib in metastatic clear cell renal cancer

    Stewart, G. D., Powles, T., Van Neste, C., Meynert, A., O'Mahony, F., Laird, A., Deforce, D., Van Nieuwerburgh, F., Trooskens, G., Van Criekinge, W., De Meyer, T. & Harrison, D. J., 23 Mar 2016, In : Oncotarget. 7, 18, 10 p.

    Research output: Contribution to journalArticle

ID: 221604815