Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 9/2008

01-09-2008 | Original Paper

The PMAIP1 Gene on Chromosome 18 is a Candidate Tumor Suppressor Gene in Human Pancreatic Cancer

Authors: Masaharu Ishida, Makoto Sunamura, Toru Furukawa, Liviu P. Lefter, Rina Morita, Masanori Akada, Shinichi Egawa, Michiaki Unno, Akira Horii

Published in: Digestive Diseases and Sciences | Issue 9/2008

Login to get access

Abstract

Frequent loss of heterozygosity on the long arm of chromosome 18 is observed in pancreatic cancer. Previous studies suggested the existence of one or more tumor-suppressor genes other than SMAD4 on chromosome 18. To identify the candidate tumor-suppressor gene(s), we compared gene expression by cDNA microarray analyses using a pancreatic cancer cell line Panc-1 and its hybrid cell lines showing suppressed cell growth after introduction of one normal copy of chromosome 18. The microarray analyses identified 38 genes on chromosome 18 that showed differential expressional levels. Among these genes, phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1/APR/NOXA) was identified as one of the candidates for tumor suppressor. Expression vector-mediated introduction of PMAIP1 suppressed cell proliferation, and RNAi-mediated knockdown of PMAIP1 induced recovery of cell growth. These results suggest that PMAIP1 may play an important role in the progression of pancreatic cancer.
Appendix
Available only for authorised users
Literature
1.
2.
3.
Livingston EH, Welton ML, Reber HA (1991) The United States’ experience with surgery for pancreatic cancer. Int J Pancreatol 9:153–157PubMed
4.
Furukawa T, Sunamura M, Horii A (2006) Molecular mechanisms of pancreatic carcinogenesis. Cancer Sci 97:1–7PubMedCrossRef
5.
Griffin CA, Hruban RH, Morsberger LA, Ellingham T, Long PP, Jaffee EM, Hauda KM, Bohlander SK, Yeo CJ (1995) Consistent chromosome abnormalities in adenocarcinoma of the pancreas. Cancer Res 55:2394–2399PubMed
6.
Kimura M, Furukawa T, Sunamura M, Takeda K, Matsuno S, Horii A (1996) Detailed deletion mapping on chromosome arm 12q in human pancreatic adenocarcinoma: identification of a 1-cM region of common allelic loss. Genes Chromosomes Cancer 17:88–93PubMedCrossRef
7.
Fukushige S, Waldman FM, Kimura M, Abe T, Furukawa T, Sunamura M, Kobari M, Horii A (1997) Frequent gain of copy number on the long arm of chromosome 20 in human pancreatic adenocarcinoma. Genes Chromosomes Cancer 19:161–169PubMedCrossRef
8.
Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M (1988) Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53:549–554PubMedCrossRef
9.
Barton CM, Staddon SL, Hughes CM, Hall PA, O’Sullivan C, Klöppel G, Theis B, Russell RCG, Neoptolemos J, Williamson RCN, Lane DP, Lemoine NR (1991) Abnormalities of the p53 tumour suppressor gene in human pancreatic cancer. Br J Cancer 64:1076–1082PubMed
10.
Caldas C, Hahn SA, da Costa LT, Redson MS, Schutte M, Seymour AB, Weinstein CL, Hruban RH, Yeo CJ, Kem SE (1994) Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. Nat Genet 8:27–32PubMedCrossRef
11.
Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, Weinstein CL, Fischer A, Yeo CJ, Hruban RH, Kern SE (1996) DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 271:350–353PubMedCrossRef
12.
Yatsuoka T, Sunamura M, Furukawa T, Fukushige S, Yokoyama T, Inoue H, Shibuya K, Takeda K, Matsuno S, Horii A (2000) Association of poor prognosis with loss of 12q, 17p, and 18q, and concordant loss of 6q/17p and 12q/18q in human pancreatic ductal adenocarcinoma. Am J Gastroenterol 95:2080–2085PubMedCrossRef
13.
Fukushige S, Furukawa T, Satoh K, Sunamura M, Kobari M, Koizumi M, Horii A (1998) Loss of chromosome 18q is an early event in pancreatic ductal tumorigenesis. Cancer Res 58:4222–4226PubMed
14.
Inoue H, Furukawa T, Sunamura M, Takeda K, Matsuno S, Horii A (2001) Exclusion of SMAD4 mutation as an early genetic change in human pancreatic ductal tumorigenesis. Genes Chromosomes Cancer 31:295–299PubMedCrossRef
15.
Schwarte-Waldhoff I, Volpert OV, Bouck NP, Sipos B, Hahn SA, Klein-Scory S, Luttges J, Kloppel G, Graeven U, Eilert-Micus C, Hintelmann A, Schmiegel W (2000) Smad4/DPC4-mediated tumor suppression through suppression of angiogenesis. Proc Natl Acad Sci USA 97:9624–9629PubMedCrossRef
16.
Duda DG, Sunamura M, Lefter LP, Furukawa T, Yokoyama T, Yatsuoka T, Abe T, Inoue H, Motoi F, Egawa S, Matsuno S, Horii A (2003) Restoration of SMAD4 by gene therapy reverses the invasive phenotype in pancreatic adenocarcinoma cells. Oncogene 22:6857–6864PubMedCrossRef
17.
Lefter LP, Furukawa T, Sunamura M, Duda DG, Takeda K, Kotobuki N, Oshimura M, Matsuno S, Horii A (2002) Suppression of the tumorigenic phenotype by chromosome 18 transfer into pancreatic cancer cell lines. Genes Chromosomes Cancer 34:234–242PubMedCrossRef
18.
Tanaka K, Oshimura M, Kikuchi R, Seki M, Hayashi T, Miyaki M (1991) Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 5 or 18. Nature 349:340–342PubMedCrossRef
19.
Padalecki SS, Johnson-Pais TL, Killary AM, Leach RJ (2001) Chromosome 18 suppresses the tumorigenicity of prostate cancer cells. Genes Chromosomes Cancer 30:221–229PubMedCrossRef
20.
Sun C, Yamato T, Furukawa T, Ohnishi Y, Kijima H, Horii A (2001) Characterization of the mutations of the K-ras, p53, p16, and SMAD4 genes in 15 human pancreatic cancer cell lines. Oncol Rep 8:89–92PubMed
21.
Ishida M, Sunamura M, Furukawa T, Akada M, Fujimura H, Shibuya E, Egawa S, Unno M, Horii A (2007) Elucidation of the relationship of BNIP3 expression to gemcitabine chemosensitivity and prognosis. World J Gastroenterol 13:4593–4597PubMed
22.
van Golen KL, Wu ZF, Qiao XT, Bao L, Merajver SD (2000) RhoC GTPase, a novel transforming oncogene for human mammary epithelial cells that partially recapitulates the inflammatory breast cancer phenotype. Cancer Res 60:5832–5838PubMed
23.
Hata T, Furukawa T, Sunamura M, Egawa S, Motoi F, Ohmura N, Marumoto T, Saya H, Horii A (2005) RNA interference targeting aurora kinase A suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells. Cancer Res 65:2899–2905PubMedCrossRef
24.
Furukawa T, Kanai N, Shiwaku HO, Soga N, Uehara A, Horii A (2006) AURKA is one of the downstream targets of MAPK1/ERK2 in pancreatic cancer. Oncogene 25:4831–4839PubMedCrossRef
25.
Yamanaka S, Sunamura M, Furukawa T, Sun L, Lefter LP, Abe T, Yatsuoka T, Fujimura H, Shibuya E, Kotobuki N, Oshimura M, Sakurada A, Sato M, Kondo T, Matsuno S, Horii A (2004) Chromosome 12, frequently deleted in human pancreatic cancer, may encode a tumor suppressor gene that suppresses angiogenesis. Lab Invest 84:1339–1351PubMedCrossRef
26.
Tanaka K, Yanoshita R, Konishi M, Oshimura M, Maeda Y, Mori T, Miyaki M (1993) Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 1p36 region. Oncogene 8:2253–2258PubMed
27.
Kugoh H, Nakamoto H, Inoue J, Funaki K, Barrett JC, Oshimura M (2002) Multiple human chromosomes carrying tumor-suppressor functions for the mouse melanoma cell line B16F10, identified by microcell-mediated chromosome transfer. Mol Carcinog 35:148–156PubMedCrossRef
28.
Matsuura S, Tauchi H, Nakamura A, Kondo N, Sakamoto S, Endo S, Smeets D, Solder B, Belohradsky BH, Der Kaloustian VM, Oshimura M, Isomura M, Nakamura Y, Komatsu K (1998) Positional cloning of the gene for Nijmegen breakage syndrome. Nat Genet 19:179–181PubMedCrossRef
29.
Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N (2000) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288:1053–1058PubMedCrossRef
30.
Seo YW, Shin JN, Ko KH, Cha JH, Park JY, Lee BR, Yun CW, Kim YM, Seol DW, Kim DW, Yin XM, Kim TH (2003) The molecular mechanism of Noxa-induced mitochondrial dysfunction in p53-mediated death. J Biol Chem 278:48292–48299PubMedCrossRef
31.
Schuler M, Maurer U, Goldstein JC, Breitenbucher F, Hoffarth S, Waterhouse NJ, Green DR (2003) p53 triggers apoptosis in oncogene-expressing fibroblasts by the induction of Noxa and mitochondrial Bax translocation. Cell Death Differ 10:451–460PubMedCrossRef
32.
Villunger A, Michalak EM, Coultas L, Mullauer F, Bock G, Ausserlechner MJ, Adams JP, Strasser A (2003) p53- and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa. Science 302:1036–1038PubMedCrossRef
33.
Kim JY, Ahn HJ, Ryu JH, Suk K, Park JH (2004) BH3-only protein Noxa is a mediator of hypoxic cell death induced by hypoxia-inducible factor 1alpha. J Exp Med 199:113–124PubMedCrossRef
34.
Porta C, Hadj-Slimane R, Nejmeddine M, Pampin M, Tovey MG, Espert L, Alvarez S, Chelbi-Alix MK (2005) Interferons alpha and gamma induce p53-dependent and p53-independent apoptosis, respectively. Oncogene 24:605–615PubMedCrossRef
35.
Sun Y, Leaman DW (2005) Involvement of Noxa in cellular apoptotic responses to interferon, double-stranded RNA, and virus infection. J Biol Chem 280:15561–15568PubMedCrossRef
36.
Sasaki T, Sasahira T, Shimura H, Ikeda S, Kuniyasu H (2004) Effect of human Noxa on irinotecan-induced apoptosis in human gastric carcinoma cell lines. Hepatogastroenterology 51:912–915PubMed
37.
Qin JZ, Ziffra J, Stennett L, Bodner B, Bonish BK, Chaturvedi V, Bennett F, Pollock PM, Trent JM, Hendrix MJ, Rizzo P, Miele L, Nickoloff BJ (2005) Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells. Cancer Res 65:6282–6293PubMedCrossRef
38.
Fernandez Y, Verhaegen M, Miller TP, Rush JL, Steiner P, Opipari AW Jr, Lowe SW, Soengas MS (2005) Differential regulation of Noxa in normal melanocytes and melanoma cells by proteasome inhibition: therapeutic implications. Cancer Res 65:6294–6304PubMedCrossRef
39.
Perez-Galan P, Roue G, Villamor N, Montserrat E, Campo E, Colomer D (2006) The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status. Blood 107:257–264PubMedCrossRef
Metadata
Title
The PMAIP1 Gene on Chromosome 18 is a Candidate Tumor Suppressor Gene in Human Pancreatic Cancer
Authors
Masaharu Ishida
Makoto Sunamura
Toru Furukawa
Liviu P. Lefter
Rina Morita
Masanori Akada
Shinichi Egawa
Michiaki Unno
Akira Horii
Publication date
01-09-2008
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 9/2008
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-007-0154-1

Other articles of this Issue 9/2008

Digestive Diseases and Sciences 9/2008 Go to the issue

Original Paper

Disturbance of Apoptosis and DNA Synthesis by Helicobacter pylori Infection of Hepatocytes

Original Paper

Through-the-Scope, Wire-Guided Esophageal Dilation for the Treatment of Food Impaction

Letter to the Editor

High Recurrence Rates of Helicobacter pylori Infection Can Be Related to False-Positive Histologies

Original Paper

Probiotics and Blueberry Attenuate the Severity of Dextran Sulfate Sodium (DSS)-Induced Colitis

Original Paper

Prevalence and Associated Features of Gastroesophageal Reflux Symptoms in a Caucasian-Predominant Adolescent School Population

Original Paper

The Activity of Class I, II, III, and IV Alcohol Dehydrogenase (ADH) Isoenzymes and Aldehyde Dehydrogenase (ALDH) in Liver Cancer
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits