5α-reductase 1 mRNA levels are positively correlated with TRAMP mouse prostate most severe lesion scores

Alexander B. Opoku-Acheampong, Jamie N. Henningson, Amanda P. Beck, Brian L. Lindshield

Research output: Contribution to journalArticle

  • 1 Citations

Abstract

Background The contribution of 5α-reductase 1 and 5α-reductase 2 to prostate cancer development and progression is not clearly understood. TRAMP mice are a common prostate cancer model, in which 5α-reductase 1 and 5α-reductase 2 expression levels, along with prostate lesions scores, have not been investigated at different time points to further understand prostate carcinogenesis. Method/Principal findings To this end, 8-, 12-, 16-, and 20-week-old male C57BL/6TRAMP x FVB mice prostate most severe and most common lesion scores, 5α-reductase 1 and 5α-reductase 2 in situ hybridization expression, and Ki-67, androgen receptor, and apoptosis immunohistochemistry levels were measured. Levels of these markers were quantified in prostate epithelium, hyperplasia, and tumors sections. Mice developed low- to high-grade prostatic intraepithelial neoplasia at 8 weeks as the most severe and most common lesions, and moderate- and high-grade prostatic intraepithelial neoplasia at 12 and 16 weeks as the most severe lesion in all lobes. Moderately differentiated adenocarcinoma was observed at 20 weeks in all lobes. Poorly differentiated carcinoma was not observed in any lobe until 12-weeks-old. 5α- reductase 1 and 5α-reductase 2 were not significantly decreased in tumors compared to prostate epithelium and hyperplasia in all groups, while proliferation, apoptosis, and androgen receptor were either notably or significantly decreased in tumors compared with prostate epithelium and hyperplasia in most or all groups. Prostate 5αR1 levels were positively correlated with adjusted prostate most severe lesion scores. Conclusion Downregulation of androgen receptor and 5α-reductase 2, along with upregulation of 5α- reductase 1 in tumors may promote prostatic intraepithelial neoplasia and prostate cancer development in TRAMP mice.

Original languageEnglish (US)
Article numbere0175874
JournalPLoS ONE
Volume12
Issue number5
DOIs
StatePublished - May 1 2017

Fingerprint

Prostate
Oxidoreductases
Messenger RNA
neoplasms
lesions (animal)
mice
prostatic neoplasms
hyperplasia
epithelium
androgen receptors
Neoplasms
Contraception Behavior
Prostatic Intraepithelial Neoplasia
Androgen Receptors
Hyperplasia
Prostatic Neoplasms
Epithelium
apoptosis
Apoptosis
adenocarcinoma

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

5α-reductase 1 mRNA levels are positively correlated with TRAMP mouse prostate most severe lesion scores. / Opoku-Acheampong, Alexander B.; Henningson, Jamie N.; Beck, Amanda P.; Lindshield, Brian L.

In: PLoS ONE, Vol. 12, No. 5, e0175874, 01.05.2017.

Research output: Contribution to journalArticle

Opoku-Acheampong AB, Henningson JN, Beck AP, Lindshield BL. 5α-reductase 1 mRNA levels are positively correlated with TRAMP mouse prostate most severe lesion scores. PLoS ONE. 2017 May 1;12(5). e0175874. Available from, DOI: 10.1371/journal.pone.0175874

Opoku-Acheampong, Alexander B.; Henningson, Jamie N.; Beck, Amanda P.; Lindshield, Brian L. / 5α-reductase 1 mRNA levels are positively correlated with TRAMP mouse prostate most severe lesion scores.

In: PLoS ONE, Vol. 12, No. 5, e0175874, 01.05.2017.

Research output: Contribution to journalArticle

@article{b59856b61b51449b920b42a4ec8a184d,
title = "5α-reductase 1 mRNA levels are positively correlated with TRAMP mouse prostate most severe lesion scores",
abstract = "Background The contribution of 5α-reductase 1 and 5α-reductase 2 to prostate cancer development and progression is not clearly understood. TRAMP mice are a common prostate cancer model, in which 5α-reductase 1 and 5α-reductase 2 expression levels, along with prostate lesions scores, have not been investigated at different time points to further understand prostate carcinogenesis. Method/Principal findings To this end, 8-, 12-, 16-, and 20-week-old male C57BL/6TRAMP x FVB mice prostate most severe and most common lesion scores, 5α-reductase 1 and 5α-reductase 2 in situ hybridization expression, and Ki-67, androgen receptor, and apoptosis immunohistochemistry levels were measured. Levels of these markers were quantified in prostate epithelium, hyperplasia, and tumors sections. Mice developed low- to high-grade prostatic intraepithelial neoplasia at 8 weeks as the most severe and most common lesions, and moderate- and high-grade prostatic intraepithelial neoplasia at 12 and 16 weeks as the most severe lesion in all lobes. Moderately differentiated adenocarcinoma was observed at 20 weeks in all lobes. Poorly differentiated carcinoma was not observed in any lobe until 12-weeks-old. 5α- reductase 1 and 5α-reductase 2 were not significantly decreased in tumors compared to prostate epithelium and hyperplasia in all groups, while proliferation, apoptosis, and androgen receptor were either notably or significantly decreased in tumors compared with prostate epithelium and hyperplasia in most or all groups. Prostate 5αR1 levels were positively correlated with adjusted prostate most severe lesion scores. Conclusion Downregulation of androgen receptor and 5α-reductase 2, along with upregulation of 5α- reductase 1 in tumors may promote prostatic intraepithelial neoplasia and prostate cancer development in TRAMP mice.",
author = "Opoku-Acheampong, {Alexander B.} and Henningson, {Jamie N.} and Beck, {Amanda P.} and Lindshield, {Brian L.}",
year = "2017",
month = "5",
doi = "10.1371/journal.pone.0175874",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

TY - JOUR

T1 - 5α-reductase 1 mRNA levels are positively correlated with TRAMP mouse prostate most severe lesion scores

AU - Opoku-Acheampong,Alexander B.

AU - Henningson,Jamie N.

AU - Beck,Amanda P.

AU - Lindshield,Brian L.

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Background The contribution of 5α-reductase 1 and 5α-reductase 2 to prostate cancer development and progression is not clearly understood. TRAMP mice are a common prostate cancer model, in which 5α-reductase 1 and 5α-reductase 2 expression levels, along with prostate lesions scores, have not been investigated at different time points to further understand prostate carcinogenesis. Method/Principal findings To this end, 8-, 12-, 16-, and 20-week-old male C57BL/6TRAMP x FVB mice prostate most severe and most common lesion scores, 5α-reductase 1 and 5α-reductase 2 in situ hybridization expression, and Ki-67, androgen receptor, and apoptosis immunohistochemistry levels were measured. Levels of these markers were quantified in prostate epithelium, hyperplasia, and tumors sections. Mice developed low- to high-grade prostatic intraepithelial neoplasia at 8 weeks as the most severe and most common lesions, and moderate- and high-grade prostatic intraepithelial neoplasia at 12 and 16 weeks as the most severe lesion in all lobes. Moderately differentiated adenocarcinoma was observed at 20 weeks in all lobes. Poorly differentiated carcinoma was not observed in any lobe until 12-weeks-old. 5α- reductase 1 and 5α-reductase 2 were not significantly decreased in tumors compared to prostate epithelium and hyperplasia in all groups, while proliferation, apoptosis, and androgen receptor were either notably or significantly decreased in tumors compared with prostate epithelium and hyperplasia in most or all groups. Prostate 5αR1 levels were positively correlated with adjusted prostate most severe lesion scores. Conclusion Downregulation of androgen receptor and 5α-reductase 2, along with upregulation of 5α- reductase 1 in tumors may promote prostatic intraepithelial neoplasia and prostate cancer development in TRAMP mice.

AB - Background The contribution of 5α-reductase 1 and 5α-reductase 2 to prostate cancer development and progression is not clearly understood. TRAMP mice are a common prostate cancer model, in which 5α-reductase 1 and 5α-reductase 2 expression levels, along with prostate lesions scores, have not been investigated at different time points to further understand prostate carcinogenesis. Method/Principal findings To this end, 8-, 12-, 16-, and 20-week-old male C57BL/6TRAMP x FVB mice prostate most severe and most common lesion scores, 5α-reductase 1 and 5α-reductase 2 in situ hybridization expression, and Ki-67, androgen receptor, and apoptosis immunohistochemistry levels were measured. Levels of these markers were quantified in prostate epithelium, hyperplasia, and tumors sections. Mice developed low- to high-grade prostatic intraepithelial neoplasia at 8 weeks as the most severe and most common lesions, and moderate- and high-grade prostatic intraepithelial neoplasia at 12 and 16 weeks as the most severe lesion in all lobes. Moderately differentiated adenocarcinoma was observed at 20 weeks in all lobes. Poorly differentiated carcinoma was not observed in any lobe until 12-weeks-old. 5α- reductase 1 and 5α-reductase 2 were not significantly decreased in tumors compared to prostate epithelium and hyperplasia in all groups, while proliferation, apoptosis, and androgen receptor were either notably or significantly decreased in tumors compared with prostate epithelium and hyperplasia in most or all groups. Prostate 5αR1 levels were positively correlated with adjusted prostate most severe lesion scores. Conclusion Downregulation of androgen receptor and 5α-reductase 2, along with upregulation of 5α- reductase 1 in tumors may promote prostatic intraepithelial neoplasia and prostate cancer development in TRAMP mice.

UR - http://www.scopus.com/inward/record.url?scp=85018896844&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018896844&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0175874

DO - 10.1371/journal.pone.0175874

M3 - Article

VL - 12

JO - PLoS One

T2 - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 5

M1 - e0175874

ER -