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Copyright by Eunyoung Park 2007 - The University of Texas at Austin

Copyright by Eunyoung Park 2007 - The University of Texas at Austin

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List of Figures FIGURE 1.1. GENETIC ALTERATIONS ASSOCIATED WITH COLON CARCINOGENESIS. ........................................................................................................................................... 10 FIGURE 1.2. A. RETINOID METABOLISM (34) AND B. SIGNALING VIA RAR, RXR AND RARE ....................................................................................................................... 11 FIGURE 2.1. RETINOL INHIBITS THE GROWTH OF ATRA-RESISTANT HUMAN COLON CANCER CELLS. .................................................................................................. 32 FIGURE 2.2. RETINOL IS NOT METABOLIZED TO BIOACTIVE COMPOUNDS IN HCT- 15 AND SW620 CELLS BUT IS CONVERTED TO ATRA BY HCT-116 AND WIDR CELLS. ........................................................................................................................................... 34 FIGURE 2.3. RETINOL DOES NOT INDUCE RARE-CAT REPORTER GENE EXPRESSION. .................................................................................................................... 35 FIGURE 2.4. RETINOL DOES NOT ACT THROUGH RAR TO INHIBIT CELL GROWTH. ........................................................................................................................................... 36 FIGURE 2.5. RETINOL DOES NOT INDUCE APOPTOSIS OR CELLULAR DIFFERENTIATION IN ATRA-RESISTANT HUMAN COLON CANCER CELL LINES. ...... 38 FIGURE 2.6. RETINOL ALTERS CELL CYCLE PROGRESSION BUT DOES NOT INDUCE APOPTOSIS........................................................................................................................ 40 FIGURE 3.1. EFFECT OF RETINOL ON ATRA-RESISTANT COLON CANCER CELL MIGRATION AND INVASION............................................................................................. 62 FIGURE 3.2. EFFECT OF CO-TREATMENT WITH RETINOL AND CYCLOHEXIMIDE, ACTINOMYCIN D OR A PAN-RAR ANTAGONIST ON ATRA-RESISTANT COLON CANCER CELL INVASION................................................................................................. 63 FIGURE 3.3. EFFECT OF RETINOL ON MMP MRNA LEVELS. ................................... 64 FIGURE 3.4. EFFECT OF RETINOL ON MMP ACTIVITY AND PROTEIN LEVELS........ 66 FIGURE 3.5. MMP ANTIBODIES BLOCK THE INVASION OF HCT-116 AND SW620 CELLS................................................................................................................................ 67 FIGURE 3.6. EFFECT OF RETINOL ON TIMP-1 PROTEIN AND MRNA....................... 68 FIGURE 4.1. RETINOL DECREASES PI3K ACTIVITY................................................... 90 FIGURE 4.2. RETINOL DOES NOT CHANGE P110 OR P85 PROTEIN LEVELS OR P85/P110 HETERODIMERIZATION. ................................................................................. 92 FIGURE 4.3. RETINOL DECREASES PI3K ACTIVITY BY INHIBITING PI3K AND PI INTERACTION................................................................................................................... 94 FIGURE 4.4. RETINOL AND LY294002 DECREASE CELL INVASION. ......................... 95 FIGURE 4.5. RETINOL AND WORTMANNIN EXHIBIT SIMILAR ELECTROSTATIC POTENTIAL SURFACES. ................................................................................................... 97 FIGURE 5.1. AVERAGE FOOD INTAKE AND BODY WEIGHT...................................... 113 FIGURE 5.2. DIETARY VITAMIN A SUPPLEMENTATION DECREASES METASTATIC INCIDENCE; CHEMOTHERAPY DIETARY MODEL. ....................................................... 114 FIGURE 5.3. DIETARY VITAMIN A SUPPLEMENTATION REDUCES TUMOR MULTIPLICITY IN MICE SUBJECTED TO THE CHEMOPREVENTION DIETARY REGIMEN. ......................................................................................................................................... 115 FIGURE 5.4. IMMUNOHISTOCHEMICAL DATA FROM CHEMOPREVENTION STUDY116 x

FIGURE 6.1. RETINOL DECREASES PI3K ACTIVITY AND/OR MMP-2 AND -9 ACTIVITY AND INCREASES TIMP-1 SECRETION TO INHIBIT COLON CANCER METASTASIS. .................................................................................................................. 121 xi

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