Model System - EPN-PKM3
Human non-transformed epithelial prostate cells, bearing a kinase-defective Pyk2
Category:
Cells
/
Cell lines
Last revision: Jan 29, 2015
Author(s):
Kisslinger A., Tramontano D.
Contact
Name: Kisslinger Annamaria
Address: IEOS -CNR via Pansini 5, 80131 Naples Italy
Phone: +3908107464552
Email: a.kisslinger@ieos.cnr.it
Figure legend:
Microphotograph of EPN cells wild-type and EPN-PKM in standard growing condition. Magnification: x150
Origin: EPN cell line
Description
Proline-rich tyrosine kinase 2 (Pyk2) expression inversely correlates with prostate cancer degree of malignancy; in fact, it progressively decreases in increasingly high-grade adenocarcinoma until disappearing in anaplastic undifferentiated cancer. The presence of Pyk2 in normal differentiated tissue and its progressive loss in adenocarcinoma of high grade suggest that Pyk2 plays the role of an onco-suppressor gene in the prostate. To investigate the role of Pyk2 on prostate cells’s growth and functions, EPN cells were transfected with a plasmid containing PKM, a kinase-negative mutant of Pyk2.
Loss of Pyk2 kinase activity in EPN-PKM cells increases cell motility and migration in response to serum stimulation as compared with wild-type EPN cells. The migrating phenotype is associated with a consistent decrease in the expression of E-cadherin and IRS-1 and an increase in the expression of a5-integrin. In addition, loss of Pyk2 activity induces changes in actin cytoskeleton organization of prostate cells. Taken together, all these features indicate that loss of Pyk2 activity correlates to a more aggressive phenotype of prostate cancer.
In the search of new strategies to fight prostate cancer, it is crucial to identify the genes and the related molecular mechanisms inducing epithelial prostate cells to transdifferentiate into a transformed phenotype. Altered expression of such genes may determine the metastatic potential of any particular prostate tumor; thus the appearance or disappearance of motility-related molecules could be used to aid in the diagnosis and prognosis of human prostate cancer. Assays detecting genetic markers of disease progression, such as Pyk2, might provide a means of characterizing and/or predicting the metastatic potential of the prostate tumor. In this wiew, EPN cells, a line derived from human normal prostate expressing Pyk2, and EPN-PKM3 cells, an EPN clone bearing a Pyk2 kinase-negative mutant, could be an useful model system.
Culture conditions: Keratinocyte-serum free medium (SFM) ( Gibco-Brl Milan Italy)supplemented with bovine pituitary excrat (10mg/ml), epidermal growth factor EGF (10ng/ml),cholera toxin (10ng/ml), 5% foetal calf serum (FCS) (Gibco-Brl, Life technologies, Paisley Sctland UK)
Quality validation:
Yes
Validation info
The model system has been published in peer-reviewed journals
| Citations |
|---|
| Kisslinger A, Cantile M, Sparaneo G, Vitale N, Fabbrocini G, Chieffi P, Cillo C, Mancini FP, Tramontano D. cAMP and Pyk2 interact to regulate prostate cell proliferation and function. Cancer Biol Ther. 2009;8:236-42. |
| De Amicis F.,Lanzino M., Kisslinger A., Calì G., Chieffi P., Mancini F.P. and Tramontano D. Loss of proline-rich tyrosine kinase 2 function induces spreading and motility of epithelial prostate cells J Cell Physiol. 2006;209:74-80. |
| Kisslinger A, Villacci A, Cantile M, Staibano S, De Rosa G, Chieffi P, Cillo C, Tramontano D. Pyk2: A ‘‘keeper’’ of prostate identity. In: Medimond, editor.2004 Proceedings of the 12th International Congress of Endocrinology. pp 1523–1529 |
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