Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo

Ibane Abasolo; Luping Yang; Riffat Haleem; Wuhan Xiao; Ruben Pio; Frank Cuttitta; Luis M. Montuenga; James M. Kozlowski; Alfonso Calvo; Zhou Wang

doi:10.1016/S0303-7207(02)00229-0

Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo

Ibane Abasolo, Luping Yang, Riffat Haleem, Wuhan Xiao, Ruben Pio, Frank Cuttitta, Luis M. Montuenga, James M. Kozlowski, Alfonso Calvo, Zhou Wang^*

^*Corresponding author for this work

Medical Education

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

19 Scopus citations

Abstract

The expression of the gene encoding adrenomedullin (AM), a multifunctional peptide hormone, in the prostate is localized to the epithelial cells. Prostate cancer cells are derived from prostatic epithelial cells. To elucidate the potential role of the AM gene in prostate cancer progression, we have stably-transfected the PC3 human prostate cancer cell line with an AM gene expression vector. The AM-transfected PC3 sublines were studied along with parental and empty vector transfected PC3 cells as controls. The average level of AM in the conditioned media of AM-transfected cells was 0.959±0.113 nM, a physiologically relevant concentration. The ectopic expression of AM gene inhibited the proliferation of PC3 cells in culture dishes. In addition, anchorage-independent growth of the transfected sublines was virtually abolished in soft agar assays. Flow cytometry studies showed that overexpression of AM gene caused a very significant G₁/G₀ cell cycle arrest. In vivo experiments demonstrated that AM gene expression markedly inhibited the growth of xenograft tumors in nude mice. Our in vivo and in vitro studies suggest that AM could strongly suppress the malignancy of prostate cancer cells, via autocrine and/or paracrine mechanisms.

Original language	English (US)
Pages (from-to)	179-187
Number of pages	9
Journal	Molecular and Cellular Endocrinology
Volume	199
Issue number	1-2
DOIs	https://doi.org/10.1016/S0303-7207(02)00229-0
State	Published - Jan 31 2003

Funding

We thank Jomol Cyriac, Mahesh Alur, Feng Jiang, Shane Oram, and Qiuheng Zhang for critical reading of the manuscript. We also thank Mary Paniagua and the staff from the Northwestern University Flow Cytometry Facility for their assistance in the cell cycle analyses. This work was supported in part by NIH R01 DK51193, NIH P50 CA90386 Prostate Cancer SPORE, and Boehringer Ingelheim International GmbH. I.A. and L.M.M. were partially funded by Spanish Ministry of Education (CICYT PB98-0211) and Fundación Echebano. I.A. was the recipient of a Fullbright Commission grant.

Keywords

Adrenomedullin
Growth inhibition
PC3
Prostate cancer
Xenograft

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Endocrinology

UN SDGs

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

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10.1016/S0303-7207(02)00229-0

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@article{19daf539b8f94c2abe3b05c617282140,

title = "Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo",

abstract = "The expression of the gene encoding adrenomedullin (AM), a multifunctional peptide hormone, in the prostate is localized to the epithelial cells. Prostate cancer cells are derived from prostatic epithelial cells. To elucidate the potential role of the AM gene in prostate cancer progression, we have stably-transfected the PC3 human prostate cancer cell line with an AM gene expression vector. The AM-transfected PC3 sublines were studied along with parental and empty vector transfected PC3 cells as controls. The average level of AM in the conditioned media of AM-transfected cells was 0.959±0.113 nM, a physiologically relevant concentration. The ectopic expression of AM gene inhibited the proliferation of PC3 cells in culture dishes. In addition, anchorage-independent growth of the transfected sublines was virtually abolished in soft agar assays. Flow cytometry studies showed that overexpression of AM gene caused a very significant G1/G0 cell cycle arrest. In vivo experiments demonstrated that AM gene expression markedly inhibited the growth of xenograft tumors in nude mice. Our in vivo and in vitro studies suggest that AM could strongly suppress the malignancy of prostate cancer cells, via autocrine and/or paracrine mechanisms.",

keywords = "Adrenomedullin, Growth inhibition, PC3, Prostate cancer, Xenograft",

author = "Ibane Abasolo and Luping Yang and Riffat Haleem and Wuhan Xiao and Ruben Pio and Frank Cuttitta and Montuenga, \{Luis M.\} and Kozlowski, \{James M.\} and Alfonso Calvo and Zhou Wang",

note = "Funding Information: We thank Jomol Cyriac, Mahesh Alur, Feng Jiang, Shane Oram, and Qiuheng Zhang for critical reading of the manuscript. We also thank Mary Paniagua and the staff from the Northwestern University Flow Cytometry Facility for their assistance in the cell cycle analyses. This work was supported in part by NIH R01 DK51193, NIH P50 CA90386 Prostate Cancer SPORE, and Boehringer Ingelheim International GmbH. I.A. and L.M.M. were partially funded by Spanish Ministry of Education (CICYT PB98-0211) and Fundaci{\'o}n Echebano. I.A. was the recipient of a Fullbright Commission grant.",

year = "2003",

month = jan,

day = "31",

doi = "10.1016/S0303-7207(02)00229-0",

language = "English (US)",

volume = "199",

pages = "179--187",

journal = "Molecular and Cellular Endocrinology",

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T1 - Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo

AU - Abasolo, Ibane

AU - Yang, Luping

AU - Haleem, Riffat

AU - Xiao, Wuhan

AU - Pio, Ruben

AU - Cuttitta, Frank

AU - Montuenga, Luis M.

AU - Kozlowski, James M.

AU - Calvo, Alfonso

AU - Wang, Zhou

N1 - Funding Information: We thank Jomol Cyriac, Mahesh Alur, Feng Jiang, Shane Oram, and Qiuheng Zhang for critical reading of the manuscript. We also thank Mary Paniagua and the staff from the Northwestern University Flow Cytometry Facility for their assistance in the cell cycle analyses. This work was supported in part by NIH R01 DK51193, NIH P50 CA90386 Prostate Cancer SPORE, and Boehringer Ingelheim International GmbH. I.A. and L.M.M. were partially funded by Spanish Ministry of Education (CICYT PB98-0211) and Fundación Echebano. I.A. was the recipient of a Fullbright Commission grant.

PY - 2003/1/31

Y1 - 2003/1/31

N2 - The expression of the gene encoding adrenomedullin (AM), a multifunctional peptide hormone, in the prostate is localized to the epithelial cells. Prostate cancer cells are derived from prostatic epithelial cells. To elucidate the potential role of the AM gene in prostate cancer progression, we have stably-transfected the PC3 human prostate cancer cell line with an AM gene expression vector. The AM-transfected PC3 sublines were studied along with parental and empty vector transfected PC3 cells as controls. The average level of AM in the conditioned media of AM-transfected cells was 0.959±0.113 nM, a physiologically relevant concentration. The ectopic expression of AM gene inhibited the proliferation of PC3 cells in culture dishes. In addition, anchorage-independent growth of the transfected sublines was virtually abolished in soft agar assays. Flow cytometry studies showed that overexpression of AM gene caused a very significant G1/G0 cell cycle arrest. In vivo experiments demonstrated that AM gene expression markedly inhibited the growth of xenograft tumors in nude mice. Our in vivo and in vitro studies suggest that AM could strongly suppress the malignancy of prostate cancer cells, via autocrine and/or paracrine mechanisms.

AB - The expression of the gene encoding adrenomedullin (AM), a multifunctional peptide hormone, in the prostate is localized to the epithelial cells. Prostate cancer cells are derived from prostatic epithelial cells. To elucidate the potential role of the AM gene in prostate cancer progression, we have stably-transfected the PC3 human prostate cancer cell line with an AM gene expression vector. The AM-transfected PC3 sublines were studied along with parental and empty vector transfected PC3 cells as controls. The average level of AM in the conditioned media of AM-transfected cells was 0.959±0.113 nM, a physiologically relevant concentration. The ectopic expression of AM gene inhibited the proliferation of PC3 cells in culture dishes. In addition, anchorage-independent growth of the transfected sublines was virtually abolished in soft agar assays. Flow cytometry studies showed that overexpression of AM gene caused a very significant G1/G0 cell cycle arrest. In vivo experiments demonstrated that AM gene expression markedly inhibited the growth of xenograft tumors in nude mice. Our in vivo and in vitro studies suggest that AM could strongly suppress the malignancy of prostate cancer cells, via autocrine and/or paracrine mechanisms.

KW - Adrenomedullin

KW - Growth inhibition

KW - PC3

KW - Prostate cancer

KW - Xenograft

UR - https://www.scopus.com/pages/publications/0037474143

UR - https://www.scopus.com/inward/citedby.url?scp=0037474143&partnerID=8YFLogxK

U2 - 10.1016/S0303-7207(02)00229-0

DO - 10.1016/S0303-7207(02)00229-0

M3 - Article

C2 - 12581889

AN - SCOPUS:0037474143

SN - 0303-7207

VL - 199

SP - 179

EP - 187

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

IS - 1-2

ER -

Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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