TWIST1, A novel androgen-regulated gene, is a target for NKX3-1 in prostate cancer cells

Turid Eide; Håkon Ramberg; Carlotta Glackin; Donald Tindall; Kristin Austlid Taskén

doi:10.1186/1475-2867-13-4

TWIST1, A novel androgen-regulated gene, is a target for NKX3-1 in prostate cancer cells

Turid Eide, Håkon Ramberg, Carlotta Glackin, Donald Tindall, Kristin Austlid Taskén

Urology

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

Background: TWIST1 plays a key role in EMT-mediated tumor invasion and metastasis. Since bone metastasis is a hallmark of advanced prostate cancer and is detected in at least 85% of patients who die of this disease, it is of great importance to understand the regulation of the cellular signaling pathways involved in the metastatic process.Methods: Prostatic cell lines were analyzed using real time RT-PCR, chromatin immunoprecipitations (ChIP) and transfection of siRNA's and reporter constructs.Results: We report in this paper that TWIST1 is an androgen-regulated gene under tight regulation of NKX3-1. Androgens repress the expression of TWIST1 via NKX3-1, which is a prostate-specific tumor suppressor that is down-regulated in the majority of metastatic prostate tumors. We show that NKX3-1 binds to the TWIST1 promoter and that NKX3-1 over-expression reduces the activity of a TWIST1 promoter reporter construct, whereas NKX3-1 siRNA up-regulates endogenous TWIST1 mRNA in prostate cancer cells.Conclusion: Our finding that NKX3-1 represses TWIST1 expression emphasizes the functional importance of NKX3-1 in regulating TWIST1 expression during prostate cancer progression to metastatic disease.

Original language	English (US)
Article number	4
Journal	Cancer Cell International
Volume	13
Issue number	1
DOIs	https://doi.org/10.1186/1475-2867-13-4
State	Published - Jan 31 2013

Keywords

LNCaP cells
NKX3-1
Prostate cancer
TWIST1

ASJC Scopus subject areas

Oncology
Genetics
Cancer Research

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10.1186/1475-2867-13-4

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@article{11c2e7e69a044b0da7970440b2db9f65,

title = "TWIST1, A novel androgen-regulated gene, is a target for NKX3-1 in prostate cancer cells",

abstract = "Background: TWIST1 plays a key role in EMT-mediated tumor invasion and metastasis. Since bone metastasis is a hallmark of advanced prostate cancer and is detected in at least 85% of patients who die of this disease, it is of great importance to understand the regulation of the cellular signaling pathways involved in the metastatic process.Methods: Prostatic cell lines were analyzed using real time RT-PCR, chromatin immunoprecipitations (ChIP) and transfection of siRNA's and reporter constructs.Results: We report in this paper that TWIST1 is an androgen-regulated gene under tight regulation of NKX3-1. Androgens repress the expression of TWIST1 via NKX3-1, which is a prostate-specific tumor suppressor that is down-regulated in the majority of metastatic prostate tumors. We show that NKX3-1 binds to the TWIST1 promoter and that NKX3-1 over-expression reduces the activity of a TWIST1 promoter reporter construct, whereas NKX3-1 siRNA up-regulates endogenous TWIST1 mRNA in prostate cancer cells.Conclusion: Our finding that NKX3-1 represses TWIST1 expression emphasizes the functional importance of NKX3-1 in regulating TWIST1 expression during prostate cancer progression to metastatic disease.",

keywords = "LNCaP cells, NKX3-1, Prostate cancer, TWIST1",

author = "Turid Eide and H{\aa}kon Ramberg and Carlotta Glackin and Donald Tindall and Task{\'e}n, {Kristin Austlid}",

note = "Funding Information: We thank the Department of Urology at the Mayo Clinic and Foundation in Rochester, Minnesota, USA and Department of Urology at the Oslo University Hospital, Aker. Furthermore, we thank Lucy Smith (Mayo Clinic, Rochester, USA) for skilled technical assistance and Fahri Saatcioglu (University of Oslo, Norway)for providing us with anti human NKX3-1 antibody. This work was supported by The Norwegian Research Council, Health Region South East, The Norwegian Cancer Society, University of Oslo and Oslo University Hospital, Aker. DJT was supported by NIH grants CA121277, CA91956, CA125747 and the T.J. Martell Foundation.",

year = "2013",

month = jan,

day = "31",

doi = "10.1186/1475-2867-13-4",

language = "English (US)",

volume = "13",

journal = "Cancer Cell International",

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TY - JOUR

T1 - TWIST1, A novel androgen-regulated gene, is a target for NKX3-1 in prostate cancer cells

AU - Eide, Turid

AU - Ramberg, Håkon

AU - Glackin, Carlotta

AU - Tindall, Donald

AU - Taskén, Kristin Austlid

N1 - Funding Information: We thank the Department of Urology at the Mayo Clinic and Foundation in Rochester, Minnesota, USA and Department of Urology at the Oslo University Hospital, Aker. Furthermore, we thank Lucy Smith (Mayo Clinic, Rochester, USA) for skilled technical assistance and Fahri Saatcioglu (University of Oslo, Norway)for providing us with anti human NKX3-1 antibody. This work was supported by The Norwegian Research Council, Health Region South East, The Norwegian Cancer Society, University of Oslo and Oslo University Hospital, Aker. DJT was supported by NIH grants CA121277, CA91956, CA125747 and the T.J. Martell Foundation.

PY - 2013/1/31

Y1 - 2013/1/31

N2 - Background: TWIST1 plays a key role in EMT-mediated tumor invasion and metastasis. Since bone metastasis is a hallmark of advanced prostate cancer and is detected in at least 85% of patients who die of this disease, it is of great importance to understand the regulation of the cellular signaling pathways involved in the metastatic process.Methods: Prostatic cell lines were analyzed using real time RT-PCR, chromatin immunoprecipitations (ChIP) and transfection of siRNA's and reporter constructs.Results: We report in this paper that TWIST1 is an androgen-regulated gene under tight regulation of NKX3-1. Androgens repress the expression of TWIST1 via NKX3-1, which is a prostate-specific tumor suppressor that is down-regulated in the majority of metastatic prostate tumors. We show that NKX3-1 binds to the TWIST1 promoter and that NKX3-1 over-expression reduces the activity of a TWIST1 promoter reporter construct, whereas NKX3-1 siRNA up-regulates endogenous TWIST1 mRNA in prostate cancer cells.Conclusion: Our finding that NKX3-1 represses TWIST1 expression emphasizes the functional importance of NKX3-1 in regulating TWIST1 expression during prostate cancer progression to metastatic disease.

AB - Background: TWIST1 plays a key role in EMT-mediated tumor invasion and metastasis. Since bone metastasis is a hallmark of advanced prostate cancer and is detected in at least 85% of patients who die of this disease, it is of great importance to understand the regulation of the cellular signaling pathways involved in the metastatic process.Methods: Prostatic cell lines were analyzed using real time RT-PCR, chromatin immunoprecipitations (ChIP) and transfection of siRNA's and reporter constructs.Results: We report in this paper that TWIST1 is an androgen-regulated gene under tight regulation of NKX3-1. Androgens repress the expression of TWIST1 via NKX3-1, which is a prostate-specific tumor suppressor that is down-regulated in the majority of metastatic prostate tumors. We show that NKX3-1 binds to the TWIST1 promoter and that NKX3-1 over-expression reduces the activity of a TWIST1 promoter reporter construct, whereas NKX3-1 siRNA up-regulates endogenous TWIST1 mRNA in prostate cancer cells.Conclusion: Our finding that NKX3-1 represses TWIST1 expression emphasizes the functional importance of NKX3-1 in regulating TWIST1 expression during prostate cancer progression to metastatic disease.

KW - LNCaP cells

KW - NKX3-1

KW - Prostate cancer

KW - TWIST1

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JO - Cancer Cell International

JF - Cancer Cell International

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ER -

TWIST1, A novel androgen-regulated gene, is a target for NKX3-1 in prostate cancer cells

Abstract

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