M.Sc Thesis

M.Sc StudentJosephy Noam
SubjectThe Expression of the Preproenkephalin Gene in Human
DepartmentDepartment of Medicine
Supervisors ASSOCIATE PROF. Oren Zinder
DR. Gary Weisinger


BACKGROUND: The preproenkephalin (ppEnk) gene is widely expressed throughout the human nervous system. The finding of high levels of ppEnk gene expression in non-nervous system tissues and the conservation of the gene from E. coli to humans raises the possibility of more fundamental functions of the ppEnk gene-products. It has been shown that ppEnk gene expression is elevated in exponentially-growing fibroblasts but remains low in stationary cultures. This exponential growth can be significantly slowed by antisense knockout of ppEnk RNA. Scattered reports related the expression of the ppEnk gene to human malignancies, including gliomas, pheochromocytomas, and breast cancer. We investigated the expression of the ppEnk gene in colon-cancer, lung cancer and follicular lymphoma.

METHODS: We used immunohistochemical, computerized image analysis and Western Analysis. The patients own healthy tissue served as a control.

RESULTS: Immunohistochemistry showed intense cytoplasmic staining in the colon adenocarcinoma compared to the control tissue. The immunohistochemical staining of the lung cancer showed positive staining only in the well-differentiated forms, and inconclusive results in the follicular lymphoma. Western analysis of the colon adenocarcinoma showed elevated levels of four ppEnk gene-derived polypeptides. These polypeptides are novel. Further analysis revealed a pattern of increased ppEnk over-expression in well-differentiated colon adenocarcinoma compared to the poorly-differentiated form.

Conclusions: Four novel ppEnk-derived peptides are over-expressed in colon adenocarcinoma. Their over-expression depends on the level of differentiation of the tumor. Our findings indicate a role for the ppEnk gene in the differentiation and proliferation processes, which may serve as potential targets for therapeutic intervention.