15-Hydroxyprostaglandin dehydrogenase is a target of hepatocyte nuclear factor 3β and a tumor suppressor in lung cancer

Guosheng Huang, Rosana Eisenberg, Min Yan, Stefano Monti, Earl Lawrence, Pingfu Fu, Jaclyn Walbroehl, Ester Löwenberg, Todd Golub, Jaime R Merchan, Daniel G. Tenen, Sanford D. Markowitz, Balazs Halmos

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The forkhead transcription factor hepatocyte nuclear factor 3β (HNF3β) is essential in foregut development and the regulation of lung-specific genes. HNF3β expression leads to growth arrest and apoptosis in lung cancer cells and HNF3β is a candidate tumor suppressor in lung cancer. In a transcriptional profiling study using a conditional cell line system, we now identify 15-PGDH as one of the major genes induced by HNF3β expression. 15-PGDH is a critical metabolic enzyme of proliferative prostaglandins, an antagonist to cyclooxygenase-2 and a tumor suppressor in colon cancer. We confirmed the regulation of 15-PGDH expression by HNF3β in a number of systems and showed direct binding of HNF3β to 15-PGDH promoter elements. Western blotting of lung cancer cell lines and immunohistochemical examination of human lung cancer tissues found loss of 15-PGDH expression in ∼65% of lung cancers. Further studies using in vitro cell-based assays and in vivo xenograft tumorigenesis assays showed a lack of in vitro but significant in vivo tumor suppressor activity of 15-PGDH via an antiangiogenic mechanism analogous to its role in colon cancer. In summary, we identify 15-PGDH as a direct downstream effector of HNF3β and show that 15-PGDH acts as a tumor suppressor in lung cancer.

Original languageEnglish
Pages (from-to)5040-5048
Number of pages9
JournalCancer Research
Volume68
Issue number13
DOIs
StatePublished - Jul 1 2008

Fingerprint

15-hydroxyprostaglandin dehydrogenase
Hepatocyte Nuclear Factors
Lung Neoplasms
Neoplasms
Colonic Neoplasms
Forkhead Transcription Factors
Prostaglandin Antagonists
Cell Line
Cyclooxygenase 2
Heterografts
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

15-Hydroxyprostaglandin dehydrogenase is a target of hepatocyte nuclear factor 3β and a tumor suppressor in lung cancer. / Huang, Guosheng; Eisenberg, Rosana; Yan, Min; Monti, Stefano; Lawrence, Earl; Fu, Pingfu; Walbroehl, Jaclyn; Löwenberg, Ester; Golub, Todd; Merchan, Jaime R; Tenen, Daniel G.; Markowitz, Sanford D.; Halmos, Balazs.

In: Cancer Research, Vol. 68, No. 13, 01.07.2008, p. 5040-5048.

Research output: Contribution to journalArticle

Huang, G, Eisenberg, R, Yan, M, Monti, S, Lawrence, E, Fu, P, Walbroehl, J, Löwenberg, E, Golub, T, Merchan, JR, Tenen, DG, Markowitz, SD & Halmos, B 2008, '15-Hydroxyprostaglandin dehydrogenase is a target of hepatocyte nuclear factor 3β and a tumor suppressor in lung cancer', Cancer Research, vol. 68, no. 13, pp. 5040-5048. https://doi.org/10.1158/0008-5472.CAN-07-6575
Huang, Guosheng ; Eisenberg, Rosana ; Yan, Min ; Monti, Stefano ; Lawrence, Earl ; Fu, Pingfu ; Walbroehl, Jaclyn ; Löwenberg, Ester ; Golub, Todd ; Merchan, Jaime R ; Tenen, Daniel G. ; Markowitz, Sanford D. ; Halmos, Balazs. / 15-Hydroxyprostaglandin dehydrogenase is a target of hepatocyte nuclear factor 3β and a tumor suppressor in lung cancer. In: Cancer Research. 2008 ; Vol. 68, No. 13. pp. 5040-5048.
@article{ea29aa5074ea4dcda15092fd507aee76,
title = "15-Hydroxyprostaglandin dehydrogenase is a target of hepatocyte nuclear factor 3β and a tumor suppressor in lung cancer",
abstract = "The forkhead transcription factor hepatocyte nuclear factor 3β (HNF3β) is essential in foregut development and the regulation of lung-specific genes. HNF3β expression leads to growth arrest and apoptosis in lung cancer cells and HNF3β is a candidate tumor suppressor in lung cancer. In a transcriptional profiling study using a conditional cell line system, we now identify 15-PGDH as one of the major genes induced by HNF3β expression. 15-PGDH is a critical metabolic enzyme of proliferative prostaglandins, an antagonist to cyclooxygenase-2 and a tumor suppressor in colon cancer. We confirmed the regulation of 15-PGDH expression by HNF3β in a number of systems and showed direct binding of HNF3β to 15-PGDH promoter elements. Western blotting of lung cancer cell lines and immunohistochemical examination of human lung cancer tissues found loss of 15-PGDH expression in ∼65{\%} of lung cancers. Further studies using in vitro cell-based assays and in vivo xenograft tumorigenesis assays showed a lack of in vitro but significant in vivo tumor suppressor activity of 15-PGDH via an antiangiogenic mechanism analogous to its role in colon cancer. In summary, we identify 15-PGDH as a direct downstream effector of HNF3β and show that 15-PGDH acts as a tumor suppressor in lung cancer.",
author = "Guosheng Huang and Rosana Eisenberg and Min Yan and Stefano Monti and Earl Lawrence and Pingfu Fu and Jaclyn Walbroehl and Ester L{\"o}wenberg and Todd Golub and Merchan, {Jaime R} and Tenen, {Daniel G.} and Markowitz, {Sanford D.} and Balazs Halmos",
year = "2008",
month = "7",
day = "1",
doi = "10.1158/0008-5472.CAN-07-6575",
language = "English",
volume = "68",
pages = "5040--5048",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "13",

}

TY - JOUR

T1 - 15-Hydroxyprostaglandin dehydrogenase is a target of hepatocyte nuclear factor 3β and a tumor suppressor in lung cancer

AU - Huang, Guosheng

AU - Eisenberg, Rosana

AU - Yan, Min

AU - Monti, Stefano

AU - Lawrence, Earl

AU - Fu, Pingfu

AU - Walbroehl, Jaclyn

AU - Löwenberg, Ester

AU - Golub, Todd

AU - Merchan, Jaime R

AU - Tenen, Daniel G.

AU - Markowitz, Sanford D.

AU - Halmos, Balazs

PY - 2008/7/1

Y1 - 2008/7/1

N2 - The forkhead transcription factor hepatocyte nuclear factor 3β (HNF3β) is essential in foregut development and the regulation of lung-specific genes. HNF3β expression leads to growth arrest and apoptosis in lung cancer cells and HNF3β is a candidate tumor suppressor in lung cancer. In a transcriptional profiling study using a conditional cell line system, we now identify 15-PGDH as one of the major genes induced by HNF3β expression. 15-PGDH is a critical metabolic enzyme of proliferative prostaglandins, an antagonist to cyclooxygenase-2 and a tumor suppressor in colon cancer. We confirmed the regulation of 15-PGDH expression by HNF3β in a number of systems and showed direct binding of HNF3β to 15-PGDH promoter elements. Western blotting of lung cancer cell lines and immunohistochemical examination of human lung cancer tissues found loss of 15-PGDH expression in ∼65% of lung cancers. Further studies using in vitro cell-based assays and in vivo xenograft tumorigenesis assays showed a lack of in vitro but significant in vivo tumor suppressor activity of 15-PGDH via an antiangiogenic mechanism analogous to its role in colon cancer. In summary, we identify 15-PGDH as a direct downstream effector of HNF3β and show that 15-PGDH acts as a tumor suppressor in lung cancer.

AB - The forkhead transcription factor hepatocyte nuclear factor 3β (HNF3β) is essential in foregut development and the regulation of lung-specific genes. HNF3β expression leads to growth arrest and apoptosis in lung cancer cells and HNF3β is a candidate tumor suppressor in lung cancer. In a transcriptional profiling study using a conditional cell line system, we now identify 15-PGDH as one of the major genes induced by HNF3β expression. 15-PGDH is a critical metabolic enzyme of proliferative prostaglandins, an antagonist to cyclooxygenase-2 and a tumor suppressor in colon cancer. We confirmed the regulation of 15-PGDH expression by HNF3β in a number of systems and showed direct binding of HNF3β to 15-PGDH promoter elements. Western blotting of lung cancer cell lines and immunohistochemical examination of human lung cancer tissues found loss of 15-PGDH expression in ∼65% of lung cancers. Further studies using in vitro cell-based assays and in vivo xenograft tumorigenesis assays showed a lack of in vitro but significant in vivo tumor suppressor activity of 15-PGDH via an antiangiogenic mechanism analogous to its role in colon cancer. In summary, we identify 15-PGDH as a direct downstream effector of HNF3β and show that 15-PGDH acts as a tumor suppressor in lung cancer.

UR - http://www.scopus.com/inward/record.url?scp=48549087414&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=48549087414&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-07-6575

DO - 10.1158/0008-5472.CAN-07-6575

M3 - Article

C2 - 18593902

AN - SCOPUS:48549087414

VL - 68

SP - 5040

EP - 5048

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 13

ER -