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Defective signaling in a spontaneous transformation model of rat prostate epithelial cells
Author(s) -
Gajdosik Martina Srajer,
Yang DongQin,
Chatterjee Devasis,
Cross-Knorr Samuel,
Brilliant Kate E.,
Gorman Megan,
Hixson Douglas C.,
Mills David R.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb474
Subject(s) - phenotype , in vitro , prostate , biology , cancer research , malignant transformation , microbiology and biotechnology , chemistry , gene , cancer , biochemistry , genetics
We describe an in vitro model of spontaneous transformation using normal rat prostate epithelial cells (PEC) that culminates at high passage (p>85) in anchorage independent growth when plated on soft agar. High passage PEC also formed large tumors in immunodeficient mice. We identified a small subpopulation of cells derived from the high passage anchorage independent cells that migrate through soft agar and expand on the underlying plastic substratum. In addition, several antibodies generated against rat liver epithelial cells of ductal origin that react strongly with rat prostate cells were examined. OC.2 was expressed by a low percentage of low and high passage PEC but was expressed by 100% of freshly isolated soft agar invasive (SAI) cells. Conversely, OC.4 and OC.5 were expressed by a high percentage of low and high passage PEC but were absent in SAI cells. Tumorigenicity experiments demonstrated that the SAI subpopulation was considerably more tumorigenic than high passage cells, evidenced by decreased latency period and increased tumor size. Immunoblot analysis identified alterations in signaling proteins belonging to EGFR and JAK/STAT pathways between low pass, high pass and SAI cells. We are investigating the role of these pathways on the phenotype of the 3 PEC models by examining anchorage independent growth, invasion, and tumorigenicity. (Supported by COBRE grant 1P20RR17695)