Notch mediates TGFα-induced changes in epithelial differentiation during pancreatic tumorigenesis

被引：565

作者：

Miyamoto, Y

Maitra, A

Ghosh, B

Zechner, U

Argani, P

Iacobuzio-Donahue, CA

Sriuranpong, V

Iso, T

Meszoely, IM

Wolfe, MS

Hruban, RH

Ball, DW

Schmid, RM

Leach, SD ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Ctr, Dept Surg, Baltimore, MD 21287 USA

[2] Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Ctr, Dept Oncol, Baltimore, MD 21287 USA

[3] Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Ctr, Dept Pathol, Baltimore, MD 21287 USA

[4] Univ Ulm, Dept Med, Ulm, Germany

[5] Gunma Univ, Sch Med, Dept Internal Med 2, Gunma, Japan

[6] Fox Chase Canc Ctr, Dept Surg, Philadelphia, PA 19111 USA

[7] Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA

来源：

CANCER CELL | 2003年 / 3卷 / 06期

关键词：

D O I：

10.1016/S1535-6108(03)00140-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Notch signaling regulates cell fate decisions in a wide variety of adult and embryonic tissues. Here we show that Notch pathway components and Notch target genes are upregulated in invasive pancreatic cancer, as well as in pancreatic cancer precursors from both mouse and human. In mouse pancreas, ectopic Notch activation results in accumulation of nestin-positive precursor cells and expansion of metaplastic ductal epithelium, previously identified as a precursor lesion for pancreatic cancer. Notch is also activated as a direct consequence of EGF receptor activation in exocrine pancreas and is required for TGFalpha-induced changes in epithelial differentiation. These findings suggest that Notch mediates the tumor-initiating effects of TGFalpha by expanding a population of undifferentiated precursor cells.

引用

收藏

页码：565 / 576

页数：12

相关论文

共 65 条

[1] Notch signalling controls pancreatic cell differentiation [J].

Apelqvist, Å ;

Li, H ;

Sommer, L ;

Beatus, P ;

Anderson, DJ ;

Honjo, T ;

de Angelis, MH ;

Lendahl, U ;

Edlund, H .

NATURE, 1999, 400 (6747) :877-881

[2] Inhibition of NF-κB sensitizes human pancreatic carcinoma cells to apoptosis induced by etoposide (VP16) or doxorubicin [J].

Arlt, A ;

Vorndamm, J ;

Breitenbroich, M ;

Fölsch, UR ;

Kalthoff, H ;

Schmidt, WE ;

Schäfer, H .

ONCOGENE, 2001, 20 (07) :859-868

[3] Notch signaling: Cell fate control and signal integration in development [J].

Artavanis-Tsakonas, S ;

Rand, MD ;

Lake, RJ .

SCIENCE, 1999, 284 (5415) :770-776

[4] Constitutive activation of NF-κB and T-cell leukemia/lymphoma in Notch3 transgenic mice [J].

Bellavia, D ;

Campese, AF ;

Alesse, E ;

Vacca, A ;

Felli, MP ;

Balestri, A ;

Stoppacciaro, A ;

Tiveron, C ;

Tatangelo, L ;

Giovarelli, M ;

Gaetano, C ;

Ruco, L ;

Hoffman, ES ;

Hayday, AC ;

Lendahl, U ;

Frati, L ;

Gulino, A ;

Screpanti, I .

EMBO JOURNAL, 2000, 19 (13) :3337-3348

[5] Aspartate mutations in presenilin and γ-secretase inhibitors both impair Notch1 proteolysis and nuclear translocation with relative preservation of Notch1 signaling [J].

Berezovska, O ;

Jack, C ;

McLean, P ;

Aster, JC ;

Hicks, C ;

Xia, WM ;

Wolfe, MS ;

Kimberly, WT ;

Weinmaster, G ;

Selkoe, DJ ;

Hyman, BT .

JOURNAL OF NEUROCHEMISTRY, 2000, 75 (02) :583-593

[6] Notch inhibition of RAS signaling through MAP kinase phosphatase LIP-1 during C-elegans vulval development [J].

Berset, T ;

Hoier, EF ;

Battu, G ;

Canevascini, S ;

Hajnal, A .

SCIENCE, 2001, 291 (5506) :1055-1058

[7] Neoplastic transformation by truncated alleles of human NOTCH1/TAN1 and NOTCH2 [J].

Capobianco, AJ ;

Zagouras, P ;

Blaumueller, CM ;

ArtavanisTsakonas, S ;

Bishop, JM .

MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (11) :6265-6273

[8] Reciprocal regulatory interactions between the Notch and Ras signaling pathways in the Drosophila embryonic mesoderm [J].

Carmena, A ;

Buff, E ;

Halfon, MS ;

Gisselbrecht, S ;

Jiménez, F ;

Baylies, MK ;

Michelson, AM .

DEVELOPMENTAL BIOLOGY, 2002, 244 (02) :226-242

[9] Conservation of the Drosophila lateral inhibition pathway in human lung cancer: A hairy-related protein (HES-1) directly represses achaete-scute homolog-1 expression [J].

Chen, H ;

Thiagalingam, A ;

Chopra, H ;

Borges, MW ;

Feder, JN ;

Nelkin, BD ;

Baylin, SB ;

Ball, DW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (10) :5355-5360

[10] Notch-1 regulates NF-κB activity in hemopoietic progenitor cells [J].

Cheng, PY ;

Zlobin, A ;

Volgina, V ;

Gottipati, S ;

Osborne, B ;

Simel, EJ ;

Miele, L ;

Gabrilovich, DI .

JOURNAL OF IMMUNOLOGY, 2001, 167 (08) :4458-4467

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