At the same time, several human and animal studies have revealed the opposing regulation of some molecular pathways during normal aging and carcinogenesis. As opposed to normal aging, proliferating cancer cells show increased next metabolism, characterized by continuous proliferative activity and de-differentiation, they can produce embryonic proteins and are potentially immortal by escaping apoptosis [20]. In particular, apoptosis-regulating proteins show distinct expression in senescent and cancer cells featured by the downregulation of the apoptosis-inducing tumor suppressor p53 protein [21] and Fas/CD95 protein [22] and the overexpression of antiapoptotic proto-oncogene Bcl-2 in cancer as opposed to normal aging cells [23]�C[25]. Oncogenes such as Ras, transcription factors e.g.
Myc, and growth signal transduction-related tyrosine-kinase receptors e.g. members of the EGFR family are up-regulated in some cancers, while downregulated in senescent cells [26]�C[28]. Cancer development can be considered as a local, uncontrolled ��rejuvenation�� utilizing the same molecular pathways but with opposing regulation. Deregulated cell proliferation and apoptosis pathways can allow survival advantages for cancer cells against adjacent senescent cells, due to lost ability of cancer for normal aging [20]. Increased epithelial cell proliferation in the gastrointestinal tract can be seen not only in colorectal cancer, but also in embryonic and juvenile development. An essential pathway that plays fundamental roles both in gut development and in sporadic or familial colorectal cancers is the Wnt/��-catenin signaling [29]�C[30].
As we are aware, there is no study focusing on the proliferation and apoptosis regulation in the juvenile human colorectal epithelium in relation to normal aging and carcinogenesis. The purpose of this study was to analyze the proliferative and apoptotic activity in human colonic epithelium in the course of normal aging and colorectal carcinogenesis both at protein and gene expression level. Colorectal biopsies representing the juvenile AV-951 controlled growth stage, the adult healthy status and the uncontrolled colorectal cancer development were tested for potential correlations. Materials and Methods Patients and samples After informed consent, colorectal biopsy samples were taken during routine endoscopic intervention at the 2nd Department of Internal Medicine and 1st Department of Paediatrics, Semmelweis University, Budapest, Hungary.