DETECTION OF THE CANCER-RELATED GENE, CATHEPSIN B: LEVELS OF CTSB AMPLIFCATION IN THE INTERPHASE NUCLEI OF BARRETT'S ESOPHAGEAL ADENOCARCINOMA FROZEN TISSUE SECTIONS
Chun, Sang (Tony) Y.
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The cathepsin B gene (CTSB) encodes a lysosomal proteinase that has been implicated in facilitating tumor metastasis. Cathepsin B has been shown to be over-expressed in various tumors, especially along the most invasive edges of a tumor, and is believed to activate a proteolytic cascade that degrades the basement membrane, thereby facilitating tumor progression. Cathepsin B has been shown to be over-expressed in tumors of the lung, prostate, colon, stomach, breast, and esophagus. One theory of tumor progression suggests that the over-expression of cathepsin B may arise from a decrease in regulation by its endogenous inhibitors, the cysteine proteinase inhibitors. In this thesis, frozen tissue sections of normal squamous epithelium, Barrett's epithelium, and esophageal adenocarcinoma of a patient were qualitatively analyzed using interphase fluorescence in situ hybridization for the level of cathepsin B amplification. It was found that normal squamous tissue sections demonstrated low-levels of CTSB amplification. However, both Barrett's esophagus and tumor tissues showed increasing levels of CTSB amplification in the interphase nuclei. These results correlate favorably with current theories on tumor progression, specifically involving cathepsin B.