Abstract | BACKGROUND: RESULTS: Axl labeling was present in 54 of 99 (55%), and was absent in 45 of 99 (45%) cases, respectively. Axl expression in pancreatic cancer was significantly associated with lymph node metastases (p < 0.01), and a shorter median survival (12 versus 18 months, p < 0.01), than in tumors with negative labeling. Stable knockdown of Axl resulted in significant reduction in cell viability (p < 0.001), anchorage independent growth (p = 0.0031), as well as attenuation of migratory (p < 0.001) and invasive properties (p < 0.005), compared to vector-transfected cells. Profound inhibition of p42/p44 MAP kinase and PI-3kinase/Akt effector pathways was observed in MIAPaCa-2 cells with loss of Axl function. The reduction in invasion and migration upon Axl knockdown was mirrored by a decrease in the amounts of activated ( GTP-bound) GTPase proteins Rho and Rac, significant downregulation in transcript levels of the epithelial mesenchymal transition (EMT)-associated transcription factors slug, snail and twist, and significant decrease in matrix metalloproteinase MMP-9 mRNA levels. MATERIALS: The immunohistochemical expression of Axl protein was assessed in a panel of 99 archival pancreatic cancers. Endogenous Axl expression was stably downregulated by lentiviral short hairpin shRNA directed against AXL mRNA in MIAPaCa-2 cells, and the effects on cell viability, anchorage independent growth, invasion, migration and intracellular effector pathways was assessed, by comparing to lentiviral vector-transfected cells. CONCLUSION:
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Authors | Jan-Bart M Koorstra, Collins A Karikari, Georg Feldmann, Savita Bisht, Pamela Leal Rojas, G Johan A Offerhaus, Hector Alvarez, Anirban Maitra |
Journal | Cancer biology & therapy
(Cancer Biol Ther)
Vol. 8
Issue 7
Pg. 618-26
(Apr 2009)
ISSN: 1555-8576 [Electronic] United States |
PMID | 19252414
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Oncogene Proteins
- Proto-Oncogene Proteins
- RNA, Small Interfering
- Receptor Protein-Tyrosine Kinases
- Axl Receptor Tyrosine Kinase
- AXL protein, human
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Topics |
- Carcinoma, Pancreatic Ductal
(enzymology, genetics, therapy)
- Cell Growth Processes
(physiology)
- Cell Line, Tumor
- Cell Movement
(physiology)
- Female
- Humans
- Immunohistochemistry
- Lymphatic Metastasis
- Male
- Neoplasm Invasiveness
- Oncogene Proteins
(antagonists & inhibitors, biosynthesis, genetics)
- Pancreatic Neoplasms
(enzymology, genetics, pathology, therapy)
- Prognosis
- Proto-Oncogene Proteins
- RNA, Small Interfering
(genetics)
- Receptor Protein-Tyrosine Kinases
(antagonists & inhibitors, biosynthesis, genetics)
- Axl Receptor Tyrosine Kinase
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