Gene expression profiling of microdissected pancreatic ductal carcinomas using high-density DNA microarrays

被引:177
作者
Grützmann, R
Pilarsky, C
Ammerpohl, O
Lüttges, J
Böhme, A
Sipos, B
Foerder, M
Alldinger, I
Jahnke, B
Schackert, HK
Kalthoff, H
Kremer, B
Klöppel, G
Saeger, HD
机构
[1] Tech Univ Dresden, Dept Visceral Thorac & Vasc Surg, Univ Hosp Carl Gustav Carus, D-01307 Dresden, Germany
[2] Univ Schleswig Holstein, Clin Gen & Thorac Surg, Kiel, Germany
[3] Univ Schleswig Holstein, Dept Pathol, Kiel, Germany
[4] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Surg Res, D-8027 Dresden, Germany
[5] Univ Schleswig Holstein, Dept Gen Surg, Kiel, Germany
来源
NEOPLASIA | 2004年 / 6卷 / 05期
关键词
pancreatic cancer; microarray; microdissection; IRAK1; MCM7;
D O I
10.1593/neo.04295
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of malignancy-related death and is the eighth most common cancer with the lowest overall 5-year relative survival rate. To identify new molecular markers and candidates for new therapeutic regimens, we investigated the gene expression profile of microdissected cells from 11 normal pancreatic ducts, 14 samples of PDAC, and 4 well-characterized pancreatic cancer cell lines using the Affymetrix U133 GeneChip set. RNA was extracted from microdissected samples and cell lines, amplified, and labeled using a repetitive in vitro transcription protocol. Differentially expressed genes were identified using the significance analysis of microarrays program. We found 616 differentially expressed genes. Within these, 140 were also identified in PDAC by others, such as Galectin-1, Galectin-3, and MT-SP2. We validated the differential expression of several genes (e.g., CENPF, MCM2, MCM7, RAMP, IRAK1, and PTTG1) in PDAC by immunohistochemistry and reverse transcription polymerase chain reaction. We present a whole genome expression study of microdissected tissues from PDAC, from microdissected normal ductal pancreatic cells and pancreatic cancer cell lines using high-density microarrays. Within the panel of genes, we identified novel differentially expressed genes, which have not been associated with the pathogenesis of PDAC before.
引用
收藏
页码:611 / 622
页数:12
相关论文
共 60 条
  • [1] MOST HUMAN CARCINOMAS OF THE EXOCRINE PANCREAS CONTAIN MUTANT C-K-RAS GENES
    ALMOGUERA, C
    SHIBATA, D
    FORRESTER, K
    MARTIN, J
    ARNHEIM, N
    PERUCHO, M
    [J]. CELL, 1988, 53 (04) : 549 - 554
  • [2] Argani P, 2001, CANCER RES, V61, P4320
  • [3] Pancreatic cancer biology and genetics
    Bardeesy, N
    DePinho, RA
    [J]. NATURE REVIEWS CANCER, 2002, 2 (12) : 897 - 909
  • [4] Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis
    Bernal, JA
    Luna, R
    Espina, A
    Lázaro, I
    Ramos-Morales, F
    Romero, F
    Arias, C
    Silva, A
    Tortolero, M
    Pintor-Toro, JA
    [J]. NATURE GENETICS, 2002, 32 (02) : 306 - 311
  • [5] Cloning and expression of a novel nuclear matrix-associated protein that is regulated during the retinoic acid-induced neuronal differentiation
    Cheung, WMW
    Chu, AH
    Chu, PWK
    Ip, NY
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (20) : 17083 - 17091
  • [6] Molecular alterations in pancreatic carcinoma: expression profiling shows that dysregulated expression of S100 genes is highly prevalent
    Crnogorac-Jurcevic, T
    Missiaglia, E
    Blaveri, E
    Gangeswaran, R
    Jones, M
    Terris, B
    Costello, F
    Neoptolemos, JP
    Lemoine, NR
    [J]. JOURNAL OF PATHOLOGY, 2003, 201 (01) : 63 - 74
  • [7] Expression profiling of microdissected pancreatic adenocarcinomas
    Crnogorac-Jurcevic, T
    Efthimiou, E
    Nielsen, T
    Loader, J
    Terris, B
    Stamp, G
    Baron, A
    Scarpa, A
    Lemoine, NR
    [J]. ONCOGENE, 2002, 21 (29) : 4587 - 4594
  • [8] Gene expression profiles of pancreatic cancer and stromal desmoplasia
    Crnogorac-Jurcevic, T
    Efthimiou, E
    Capelli, P
    Blaveri, E
    Baron, A
    Terris, B
    Jones, M
    Tyson, K
    Bassi, C
    Scarpa, A
    Lemoine, NR
    [J]. ONCOGENE, 2001, 20 (50) : 7437 - 7446
  • [9] Clinical relevance of cyclin B1 overexpression in laryngeal squamous cell carcinoma
    Dong, YY
    Sui, L
    Watanabe, Y
    Sugimoto, K
    Tokuda, M
    [J]. CANCER LETTERS, 2002, 177 (01) : 13 - 19
  • [10] Decrease and gain of gene expression are equally discriminatory markers for prostate carcinoma -: A gene expression analysis on total and microdissected prostate tissue
    Ernst, T
    Hergenhahn, M
    Kenzelmann, M
    Cohen, CD
    Bonrouhi, M
    Weninger, A
    Klären, R
    Gröne, EF
    Wiesel, M
    Güdemann, C
    Küster, J
    Schott, W
    Staehler, G
    Kretzler, M
    Hollstein, M
    Gröne, HJ
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2002, 160 (06) : 2169 - 2180