Estrogen and estrogen receptor alpha promotes malignancy and osteoblastic tumorigenesis in prostate cancer

Sweta Mishra; Qin Tai; Xiang Gu; James Schmitz; Ashley Poullard; Roberto J. Fajardo; Devalingam Mahalingam; Xiaodong Chen; Xueqiong Zhu; Lu Zhe Sun

doi:10.18632/oncotarget.6317

Estrogen and estrogen receptor alpha promotes malignancy and osteoblastic tumorigenesis in prostate cancer

Sweta Mishra, Qin Tai, Xiang Gu, James Schmitz, Ashley Poullard, Roberto J. Fajardo, Devalingam Mahalingam, Xiaodong Chen, Xueqiong Zhu, Lu Zhe Sun^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

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

50 Scopus citations

Abstract

The role of estrogen signaling in regulating prostate tumorigenesis is relatively underexplored. Although, an increasing body of evidence has linked estrogen receptor beta (ERβ) to prostate cancer, the function of estrogen receptor alpha (ER') in prostate cancer is not very well studied. We have discovered a novel role of ER' in the pathogenesis of prostate tumors. Here, we show that prostate cancer cells express ER' and estrogen induces oncogenic properties in prostate cancer cells through ER'. Importantly, ER' knockdown in the human prostate cancer PacMetUT1 cells as well as pharmacological inhibition of ER' with ICI 182,780 inhibited osteoblastic lesion formation and lung metastasis in vivo. Co-culture of pre-osteoblasts with cancer cells showed a significant induction of osteogenic markers in the pre-osteoblasts, which was attenuated by knockdown of ER' in cancer cells suggesting that estrogen/ER' signaling promotes crosstalk between cancer and osteoblastic progenitors to stimulate osteoblastic tumorigenesis. These results suggest that ER' expression in prostate cancer cells is essential for osteoblastic lesion formation and lung metastasis. Thus, inhibition of ER' signaling in prostate cancer cells may be a novel therapeutic strategy to inhibit the osteoblastic lesion development as well as lung metastasis in patients with advanced prostate cancer.

Original language	English (US)
Pages (from-to)	44388-44402
Number of pages	15
Journal	Oncotarget
Volume	6
Issue number	42
DOIs	https://doi.org/10.18632/oncotarget.6317
State	Published - 2015

Funding

This study was in part supported by RP120290- IIRA from Cancer Prevention and Research Institute of Texas (CPRIT), and R01CA172886 from NIH, and the Cancer Therapy and Research Center at the University of Texas Health Science Center at San Antonio (UTHSCSA) through the NCI Cancer Center Support Grant 2 P30 CA054174. We thank the institutional cores of Optical Imaging, Pathology, Micro-Computed Tomography for their assistance in obtaining part of the presented data. The authors also thank Dr. Brian Rabinovich at MD Anderson Cancer Center for the pLV411G effLuc-flag- IRES-hrGFP vector, Dr. John A Copland for the lentiviral ERa shRNA constructs and Dr. Scott Lucia at University of Colorado Health Science Center for providing us with BPH-1 cells.

Keywords

Bone
Estrogen
Estrogen receptor
Metastasis
Osteoblastic
Prostate cancer

ASJC Scopus subject areas

Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.6317

Cite this

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title = "Estrogen and estrogen receptor alpha promotes malignancy and osteoblastic tumorigenesis in prostate cancer",

abstract = "The role of estrogen signaling in regulating prostate tumorigenesis is relatively underexplored. Although, an increasing body of evidence has linked estrogen receptor beta (ERβ) to prostate cancer, the function of estrogen receptor alpha (ER') in prostate cancer is not very well studied. We have discovered a novel role of ER' in the pathogenesis of prostate tumors. Here, we show that prostate cancer cells express ER' and estrogen induces oncogenic properties in prostate cancer cells through ER'. Importantly, ER' knockdown in the human prostate cancer PacMetUT1 cells as well as pharmacological inhibition of ER' with ICI 182,780 inhibited osteoblastic lesion formation and lung metastasis in vivo. Co-culture of pre-osteoblasts with cancer cells showed a significant induction of osteogenic markers in the pre-osteoblasts, which was attenuated by knockdown of ER' in cancer cells suggesting that estrogen/ER' signaling promotes crosstalk between cancer and osteoblastic progenitors to stimulate osteoblastic tumorigenesis. These results suggest that ER' expression in prostate cancer cells is essential for osteoblastic lesion formation and lung metastasis. Thus, inhibition of ER' signaling in prostate cancer cells may be a novel therapeutic strategy to inhibit the osteoblastic lesion development as well as lung metastasis in patients with advanced prostate cancer.",

keywords = "Bone, Estrogen, Estrogen receptor, Metastasis, Osteoblastic, Prostate cancer",

author = "Sweta Mishra and Qin Tai and Xiang Gu and James Schmitz and Ashley Poullard and Fajardo, {Roberto J.} and Devalingam Mahalingam and Xiaodong Chen and Xueqiong Zhu and Sun, {Lu Zhe}",

note = "Funding Information: This study was in part supported by RP120290- IIRA from Cancer Prevention and Research Institute of Texas (CPRIT), and R01CA172886 from NIH, and the Cancer Therapy and Research Center at the University of Texas Health Science Center at San Antonio (UTHSCSA) through the NCI Cancer Center Support Grant 2 P30 CA054174. We thank the institutional cores of Optical Imaging, Pathology, Micro-Computed Tomography for their assistance in obtaining part of the presented data. The authors also thank Dr. Brian Rabinovich at MD Anderson Cancer Center for the pLV411G effLuc-flag- IRES-hrGFP vector, Dr. John A Copland for the lentiviral ERa shRNA constructs and Dr. Scott Lucia at University of Colorado Health Science Center for providing us with BPH-1 cells.",

year = "2015",

doi = "10.18632/oncotarget.6317",

language = "English (US)",

volume = "6",

pages = "44388--44402",

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T1 - Estrogen and estrogen receptor alpha promotes malignancy and osteoblastic tumorigenesis in prostate cancer

AU - Mishra, Sweta

AU - Tai, Qin

AU - Gu, Xiang

AU - Schmitz, James

AU - Poullard, Ashley

AU - Fajardo, Roberto J.

AU - Mahalingam, Devalingam

AU - Chen, Xiaodong

AU - Zhu, Xueqiong

AU - Sun, Lu Zhe

N1 - Funding Information: This study was in part supported by RP120290- IIRA from Cancer Prevention and Research Institute of Texas (CPRIT), and R01CA172886 from NIH, and the Cancer Therapy and Research Center at the University of Texas Health Science Center at San Antonio (UTHSCSA) through the NCI Cancer Center Support Grant 2 P30 CA054174. We thank the institutional cores of Optical Imaging, Pathology, Micro-Computed Tomography for their assistance in obtaining part of the presented data. The authors also thank Dr. Brian Rabinovich at MD Anderson Cancer Center for the pLV411G effLuc-flag- IRES-hrGFP vector, Dr. John A Copland for the lentiviral ERa shRNA constructs and Dr. Scott Lucia at University of Colorado Health Science Center for providing us with BPH-1 cells.

PY - 2015

Y1 - 2015

N2 - The role of estrogen signaling in regulating prostate tumorigenesis is relatively underexplored. Although, an increasing body of evidence has linked estrogen receptor beta (ERβ) to prostate cancer, the function of estrogen receptor alpha (ER') in prostate cancer is not very well studied. We have discovered a novel role of ER' in the pathogenesis of prostate tumors. Here, we show that prostate cancer cells express ER' and estrogen induces oncogenic properties in prostate cancer cells through ER'. Importantly, ER' knockdown in the human prostate cancer PacMetUT1 cells as well as pharmacological inhibition of ER' with ICI 182,780 inhibited osteoblastic lesion formation and lung metastasis in vivo. Co-culture of pre-osteoblasts with cancer cells showed a significant induction of osteogenic markers in the pre-osteoblasts, which was attenuated by knockdown of ER' in cancer cells suggesting that estrogen/ER' signaling promotes crosstalk between cancer and osteoblastic progenitors to stimulate osteoblastic tumorigenesis. These results suggest that ER' expression in prostate cancer cells is essential for osteoblastic lesion formation and lung metastasis. Thus, inhibition of ER' signaling in prostate cancer cells may be a novel therapeutic strategy to inhibit the osteoblastic lesion development as well as lung metastasis in patients with advanced prostate cancer.

AB - The role of estrogen signaling in regulating prostate tumorigenesis is relatively underexplored. Although, an increasing body of evidence has linked estrogen receptor beta (ERβ) to prostate cancer, the function of estrogen receptor alpha (ER') in prostate cancer is not very well studied. We have discovered a novel role of ER' in the pathogenesis of prostate tumors. Here, we show that prostate cancer cells express ER' and estrogen induces oncogenic properties in prostate cancer cells through ER'. Importantly, ER' knockdown in the human prostate cancer PacMetUT1 cells as well as pharmacological inhibition of ER' with ICI 182,780 inhibited osteoblastic lesion formation and lung metastasis in vivo. Co-culture of pre-osteoblasts with cancer cells showed a significant induction of osteogenic markers in the pre-osteoblasts, which was attenuated by knockdown of ER' in cancer cells suggesting that estrogen/ER' signaling promotes crosstalk between cancer and osteoblastic progenitors to stimulate osteoblastic tumorigenesis. These results suggest that ER' expression in prostate cancer cells is essential for osteoblastic lesion formation and lung metastasis. Thus, inhibition of ER' signaling in prostate cancer cells may be a novel therapeutic strategy to inhibit the osteoblastic lesion development as well as lung metastasis in patients with advanced prostate cancer.

KW - Bone

KW - Estrogen

KW - Estrogen receptor

KW - Metastasis

KW - Osteoblastic

KW - Prostate cancer

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SN - 1949-2553

VL - 6

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JO - Oncotarget

JF - Oncotarget

IS - 42

ER -

Estrogen and estrogen receptor alpha promotes malignancy and osteoblastic tumorigenesis in prostate cancer

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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