SIRT1 is significantly elevated in mouse and human prostate cancer

Derek M. Huffman, William E. Grizzle, Marcas M. Bamman, Jeong Su Kim, Isam A. Eltoum, Ada Elgavish, Tim R. Nagy

Research output: Contribution to journalArticle

321 Citations (Scopus)

Abstract

Evidence suggests that the histone deacetylase, SIRT1, is a mediator of life span extension by calorie restriction; however, SIRT1 may paradoxically increase the risk of cancer. To better understand the relationship among SIRT1, energy balance, and cancer, two experiments were done. First, a transgenic mouse model of prostate cancer (transgenic adenocarcinoma of mouse prostate; TRAMP) was used to determine the role of energy balance on SIRT1 expression and the effect of cancer stage on SIRT1 and hypermethylated in cancer-1 (HIC-1). Second, immunohistochemistry was done on human prostate tumors to determine if SIRT1 was differentially expressed in tumor cells versus uninvolved cells. Results show that SIRT1 is not increased in the dorsolateral prostate (DLP) of calorie-restricted mice during carcinogenesis. In contrast, when examined in the DLP as a function of pathologic score, SIRT1 was significantly elevated in mice with poorly differentiated adenocarcinomas compared with those with less-advanced disease. HIC-1, which has been shown to regulate SIRT1 levels, was markedly reduced in the same tumors, suggesting that a reduction in HIC-1 may be in part responsible for the increased expression of SIRT1 in prostatic adenocarcinomas. Furthermore, immunostaining of human prostate tumors showed that cancer cells had greater SIRT1 expression than uninvolved cells. In conclusion, DLP SIRT1 expression from calorie-restricted mice was not altered during carcinogenesis. However, SIRT1 expression was increased in mice with poorly differentiated adenocarcinomas and in human prostate cancer cells. Because SIRT1 may function as a tumor promoter, these results suggest that SIRT1 should be considered as a potential therapeutic target for prostate cancer.

Original languageEnglish (US)
Pages (from-to)6612-6618
Number of pages7
JournalCancer Research
Volume67
Issue number14
DOIs
StatePublished - Jul 15 2007
Externally publishedYes

Fingerprint

Prostatic Neoplasms
Prostate
Neoplasms
Adenocarcinoma
Transgenic Mice
Carcinogenesis
Histone Deacetylases
Life Expectancy
Carcinogens
Immunohistochemistry

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Huffman, D. M., Grizzle, W. E., Bamman, M. M., Kim, J. S., Eltoum, I. A., Elgavish, A., & Nagy, T. R. (2007). SIRT1 is significantly elevated in mouse and human prostate cancer. Cancer Research, 67(14), 6612-6618. https://doi.org/10.1158/0008-5472.CAN-07-0085

SIRT1 is significantly elevated in mouse and human prostate cancer. / Huffman, Derek M.; Grizzle, William E.; Bamman, Marcas M.; Kim, Jeong Su; Eltoum, Isam A.; Elgavish, Ada; Nagy, Tim R.

In: Cancer Research, Vol. 67, No. 14, 15.07.2007, p. 6612-6618.

Research output: Contribution to journalArticle

Huffman, DM, Grizzle, WE, Bamman, MM, Kim, JS, Eltoum, IA, Elgavish, A & Nagy, TR 2007, 'SIRT1 is significantly elevated in mouse and human prostate cancer', Cancer Research, vol. 67, no. 14, pp. 6612-6618. https://doi.org/10.1158/0008-5472.CAN-07-0085
Huffman DM, Grizzle WE, Bamman MM, Kim JS, Eltoum IA, Elgavish A et al. SIRT1 is significantly elevated in mouse and human prostate cancer. Cancer Research. 2007 Jul 15;67(14):6612-6618. https://doi.org/10.1158/0008-5472.CAN-07-0085
Huffman, Derek M. ; Grizzle, William E. ; Bamman, Marcas M. ; Kim, Jeong Su ; Eltoum, Isam A. ; Elgavish, Ada ; Nagy, Tim R. / SIRT1 is significantly elevated in mouse and human prostate cancer. In: Cancer Research. 2007 ; Vol. 67, No. 14. pp. 6612-6618.
@article{c8584665b2a7479fbfbc0285690e86e2,
title = "SIRT1 is significantly elevated in mouse and human prostate cancer",
abstract = "Evidence suggests that the histone deacetylase, SIRT1, is a mediator of life span extension by calorie restriction; however, SIRT1 may paradoxically increase the risk of cancer. To better understand the relationship among SIRT1, energy balance, and cancer, two experiments were done. First, a transgenic mouse model of prostate cancer (transgenic adenocarcinoma of mouse prostate; TRAMP) was used to determine the role of energy balance on SIRT1 expression and the effect of cancer stage on SIRT1 and hypermethylated in cancer-1 (HIC-1). Second, immunohistochemistry was done on human prostate tumors to determine if SIRT1 was differentially expressed in tumor cells versus uninvolved cells. Results show that SIRT1 is not increased in the dorsolateral prostate (DLP) of calorie-restricted mice during carcinogenesis. In contrast, when examined in the DLP as a function of pathologic score, SIRT1 was significantly elevated in mice with poorly differentiated adenocarcinomas compared with those with less-advanced disease. HIC-1, which has been shown to regulate SIRT1 levels, was markedly reduced in the same tumors, suggesting that a reduction in HIC-1 may be in part responsible for the increased expression of SIRT1 in prostatic adenocarcinomas. Furthermore, immunostaining of human prostate tumors showed that cancer cells had greater SIRT1 expression than uninvolved cells. In conclusion, DLP SIRT1 expression from calorie-restricted mice was not altered during carcinogenesis. However, SIRT1 expression was increased in mice with poorly differentiated adenocarcinomas and in human prostate cancer cells. Because SIRT1 may function as a tumor promoter, these results suggest that SIRT1 should be considered as a potential therapeutic target for prostate cancer.",
author = "Huffman, {Derek M.} and Grizzle, {William E.} and Bamman, {Marcas M.} and Kim, {Jeong Su} and Eltoum, {Isam A.} and Ada Elgavish and Nagy, {Tim R.}",
year = "2007",
month = "7",
day = "15",
doi = "10.1158/0008-5472.CAN-07-0085",
language = "English (US)",
volume = "67",
pages = "6612--6618",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "14",

}

TY - JOUR

T1 - SIRT1 is significantly elevated in mouse and human prostate cancer

AU - Huffman, Derek M.

AU - Grizzle, William E.

AU - Bamman, Marcas M.

AU - Kim, Jeong Su

AU - Eltoum, Isam A.

AU - Elgavish, Ada

AU - Nagy, Tim R.

PY - 2007/7/15

Y1 - 2007/7/15

N2 - Evidence suggests that the histone deacetylase, SIRT1, is a mediator of life span extension by calorie restriction; however, SIRT1 may paradoxically increase the risk of cancer. To better understand the relationship among SIRT1, energy balance, and cancer, two experiments were done. First, a transgenic mouse model of prostate cancer (transgenic adenocarcinoma of mouse prostate; TRAMP) was used to determine the role of energy balance on SIRT1 expression and the effect of cancer stage on SIRT1 and hypermethylated in cancer-1 (HIC-1). Second, immunohistochemistry was done on human prostate tumors to determine if SIRT1 was differentially expressed in tumor cells versus uninvolved cells. Results show that SIRT1 is not increased in the dorsolateral prostate (DLP) of calorie-restricted mice during carcinogenesis. In contrast, when examined in the DLP as a function of pathologic score, SIRT1 was significantly elevated in mice with poorly differentiated adenocarcinomas compared with those with less-advanced disease. HIC-1, which has been shown to regulate SIRT1 levels, was markedly reduced in the same tumors, suggesting that a reduction in HIC-1 may be in part responsible for the increased expression of SIRT1 in prostatic adenocarcinomas. Furthermore, immunostaining of human prostate tumors showed that cancer cells had greater SIRT1 expression than uninvolved cells. In conclusion, DLP SIRT1 expression from calorie-restricted mice was not altered during carcinogenesis. However, SIRT1 expression was increased in mice with poorly differentiated adenocarcinomas and in human prostate cancer cells. Because SIRT1 may function as a tumor promoter, these results suggest that SIRT1 should be considered as a potential therapeutic target for prostate cancer.

AB - Evidence suggests that the histone deacetylase, SIRT1, is a mediator of life span extension by calorie restriction; however, SIRT1 may paradoxically increase the risk of cancer. To better understand the relationship among SIRT1, energy balance, and cancer, two experiments were done. First, a transgenic mouse model of prostate cancer (transgenic adenocarcinoma of mouse prostate; TRAMP) was used to determine the role of energy balance on SIRT1 expression and the effect of cancer stage on SIRT1 and hypermethylated in cancer-1 (HIC-1). Second, immunohistochemistry was done on human prostate tumors to determine if SIRT1 was differentially expressed in tumor cells versus uninvolved cells. Results show that SIRT1 is not increased in the dorsolateral prostate (DLP) of calorie-restricted mice during carcinogenesis. In contrast, when examined in the DLP as a function of pathologic score, SIRT1 was significantly elevated in mice with poorly differentiated adenocarcinomas compared with those with less-advanced disease. HIC-1, which has been shown to regulate SIRT1 levels, was markedly reduced in the same tumors, suggesting that a reduction in HIC-1 may be in part responsible for the increased expression of SIRT1 in prostatic adenocarcinomas. Furthermore, immunostaining of human prostate tumors showed that cancer cells had greater SIRT1 expression than uninvolved cells. In conclusion, DLP SIRT1 expression from calorie-restricted mice was not altered during carcinogenesis. However, SIRT1 expression was increased in mice with poorly differentiated adenocarcinomas and in human prostate cancer cells. Because SIRT1 may function as a tumor promoter, these results suggest that SIRT1 should be considered as a potential therapeutic target for prostate cancer.

UR - http://www.scopus.com/inward/record.url?scp=34547100073&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547100073&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-07-0085

DO - 10.1158/0008-5472.CAN-07-0085

M3 - Article

VL - 67

SP - 6612

EP - 6618

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 14

ER -