Targets of Wnt/ß-catenin transcription in penile carcinoma.

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.

• Authors: Manit Arya, Christopher Thrasivoulou, Rui Henrique, Michael Millar, Ruth Hamblin, Reena Davda, Kristina Aare, John R Masters, Calum Thomson, Asif Muneer, Hitendra R H Patel, Aamir Ahmed
• Journal: PloS one (PLoS One) Vol. 10 Issue 4 Pg. e0124395 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25901368 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD1
• Neoplasm Proteins
• Proto-Oncogene Proteins c-myc
• WNT4 protein, human
• Wnt4 Protein
• beta Catenin
• Matrix Metalloproteinase 7

Topics

• Antigens, CD1 (metabolism)
• Case-Control Studies
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Matrix Metalloproteinase 7 (metabolism)
• Neoplasm Grading
• Neoplasm Proteins (metabolism)
• Penile Neoplasms (genetics, pathology)
• Proto-Oncogene Proteins c-myc (metabolism)
• Transcription, Genetic
• Wnt4 Protein (genetics, metabolism)
• beta Catenin (genetics, metabolism)