1. Targets of Wnt/ß-catenin transcription in penile carcinoma.
- Author
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Arya M, Thrasivoulou C, Henrique R, Millar M, Hamblin R, Davda R, Aare K, Masters JR, Thomson C, Muneer A, Patel HR, and Ahmed A
- Subjects
- Case-Control Studies, Gene Expression Regulation, Neoplastic, Humans, Male, Neoplasm Grading, Neoplasm Proteins metabolism, Penile Neoplasms pathology, Wnt4 Protein metabolism, beta Catenin metabolism, Antigens, CD1 metabolism, Matrix Metalloproteinase 7 metabolism, Penile Neoplasms genetics, Proto-Oncogene Proteins c-myc metabolism, Transcription, Genetic, Wnt4 Protein genetics, beta Catenin genetics
- Abstract
Penile squamous cell carcinoma (PeCa) is a rare malignancy and little is known regarding the molecular mechanisms involved in carcinogenesis of PeCa. The Wnt signaling pathway, with the transcription activator ß-catenin as a major transducer, is a key cellular pathway during development and in disease, particularly cancer. We have used PeCa tissue arrays and multi-fluorophore labelled, quantitative, immunohistochemistry to interrogate the expression of WNT4, a Wnt ligand, and three targets of Wnt-ß-catenin transcription activation, namely, MMP7, cyclinD1 (CD1) and c-MYC in 141 penile tissue cores from 101 unique samples. The expression of all Wnt signaling proteins tested was increased by 1.6 to 3 fold in PeCa samples compared to control tissue (normal or cancer adjacent) samples (p<0.01). Expression of all proteins, except CD1, showed a significant decrease in grade II compared to grade I tumors. High magnification, deconvolved confocal images were used to measure differences in co-localization between the four proteins. Significant (p<0.04-0.0001) differences were observed for various permutations of the combinations of proteins and state of the tissue (control, tumor grades I and II). Wnt signaling may play an important role in PeCa and proteins of the Wnt signaling network could be useful targets for diagnosis and prognostic stratification of disease.
- Published
- 2015
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