With more than 250 scientific citations, Oncomine has become an industry standard for cancer researchers. This series showcases recent scientific publications that use Oncomine in various and novel ways to further scientific research.
08 DEC 2009
Proepithelin is an autocrine growth factor for bladder cancer1.
Previous studies have shown that the secreted growth factor proepithelin (granulin, GRN) is over-expressed in a number of cancer types, including breast, ovarian, and brain.
A recent study used Oncomine™ to demonstrate that high levels of GRN are also associated with bladder cancer, and correlate with pathologic parameters such as invasion (Lovat et al., 2009).
To define the functional role of GRN in bladder cancer cells, study authors used shRNA to deplete GRN in T24 transitional cell carcinoma cells, and demonstrated the following:
- Significantly reduced GRN in both cell lysates and culture medium
- Reduction of cell proliferation in serum-deprived conditions
- Restoration of cell proliferation in presence of recombinant GRN
- Inhibition of cell migration
- Impaired activation of AKT pathway
- Impaired activation of MAPK pathway
Collectively these results suggest that GRN contributes to the activation of both the AKT and MAPK pathways, thereby promoting cell proliferation and migration/ invasion. This implicates proepithelin as a participant in the transition from a non-invasive to an invasive phenotype and may represent a molecular target for bladder cancer, as well as for other solid tumors.
Figure 1: Oncomine gene summary across 500+ studies reveals high GRN expression (red squares) in a number of previously reported histologies, including breast, ovarian, and brain. As Lovat et al. observed, over expression is also seen in bladder cancer.
Figure 2: As reported in the literature, proepithelin (GRN) is expressed at high levels in glioblastoma relative to normal brain.
Figure 3: Oncomine analyses showing high GRN expression in glioblastoma relative to other brain lesions (observed in multiple independent studies).
Figure 4: As the authors discovered, GRN is expressed at higher levels in bladder cancer relative to normal bladder.
Figure 5: Additionally, increased GRN expression correlates with tumor grade.
Figure 6: An association is also observed between high GRN expression and expression of MAPK kinase pathway genes (KEGG).
Figure 7: In a subsequent article2, the same group found similar results for prostate cancer, again initially using Oncomine to survey more than 2,600 analyses across all cancer types to identify cancer types that exhibit high expression of GRN in tumors vs. non-neoplastic tissue. Here are four independent studies all showing higher expression of GRN in prostate cancer vs. normal tissue.
Figure 8: Oncomine also reveals high expression of GRN in kidney cancer, in particular papillary renal cell carcinoma relative to other renal cancer types, suggesting another histology to explore involvement of proepithelin in transformation.
1 Proepithelin is an autocrine growth factor for bladder cancer.
Lovat F, Bitto A, Xu SQ, Fassan M, Goldoni S, Metalli D, Wubah V, McCue P, Serrero G, Gomella LG, Baffa R, Iozzo RV, Morrione A.
Carcinogenesis. 2009 May;30(5):861-8. Epub 2009 Feb 23.
2 Proepithelin regulates prostate cancer cell biology by promoting cell growth, migration, and anchorage-independent growth.
Monami G, Emiliozzi V, Bitto A, Lovat F, Xu SQ, Goldoni S, Fassan M, Serrero G, Gomella LG, Baffa R, Iozzo RV, Morrione A.
Am J Pathol. 2009 Mar;174(3):1037-47. Epub 2009 Jan 29.
Oncomine 4.2.3 | Data (September 2009) |
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