TY - JOUR
T1 - Activation of the serine/threonine protein kinase AKT during the progression of colorectal neoplasia
AU - Saglam, Ozlen
AU - Garrett, Christopher R.
AU - Boulware, David
AU - Sayegh, Zena
AU - Shibata, David
AU - Malafa, Mokenge
AU - Yeatman, Timothy
AU - Cheng, Jin Q.
AU - Sebti, Said
AU - Coppola, Domenico
PY - 2007/9
Y1 - 2007/9
N2 - Background: AKT has been identified as a major regulator of cell proliferation, tumorigenesis, and apoptosis. In this study, we evaluated changes in the activity of AKT during colorectal cancer (CRC) progression. Materials and Methods: We used stage-oriented human CRC tissue microarrays, including 99 invasive carcinomas, 28 tubular adenomas, and 18 samples of normal colonic mucosa.The tissue array slides were stained with a mouse monoclonal antiphospho-AKT antibody using the avidin-biotin complex method. Results: Activation of AKT was detected mostly in the invasive carcinomas. Sixty-three percent of carcinomas demonstrated strong to moderate AKT activit) Seven percent of carcinomas were phospho-AKT (p-AKT) negative, and 30% (30 of 99) were p-AKT weakly positive. Conversely, 78% of normal colonic mucosas were p-AKT negative, and only 4 samples stained weakly for p-AKI Eighty-two percent of adenomas were weakly positive for p-AKT, I was p-AKT negative, and none exhibited strong or moderate p-AKT stain. At a significance level of .05, we found that the distribution of p-AKT stain scores for cancer was shifted to the right of adenoma (P < .000 I) and normal (P < .000 I) and for adenoma was shifted to the right of normal (P < .0001). AKT activation did not correlate with tumor stage (P = .28), lymph node metastasis (P = .45), lymphatic invasion (P = .46), or distant metastasis (P = .34). Conclusion: This study shows increasing activation of AKT during CRC progression. This finding suggests a role of p-AKT in colorectal carcinogenesis and provides a rationale for using p-AKT inhibitor API-2/triciribine, which is currently under clinical investigation for the treatment of CRC.
AB - Background: AKT has been identified as a major regulator of cell proliferation, tumorigenesis, and apoptosis. In this study, we evaluated changes in the activity of AKT during colorectal cancer (CRC) progression. Materials and Methods: We used stage-oriented human CRC tissue microarrays, including 99 invasive carcinomas, 28 tubular adenomas, and 18 samples of normal colonic mucosa.The tissue array slides were stained with a mouse monoclonal antiphospho-AKT antibody using the avidin-biotin complex method. Results: Activation of AKT was detected mostly in the invasive carcinomas. Sixty-three percent of carcinomas demonstrated strong to moderate AKT activit) Seven percent of carcinomas were phospho-AKT (p-AKT) negative, and 30% (30 of 99) were p-AKT weakly positive. Conversely, 78% of normal colonic mucosas were p-AKT negative, and only 4 samples stained weakly for p-AKI Eighty-two percent of adenomas were weakly positive for p-AKT, I was p-AKT negative, and none exhibited strong or moderate p-AKT stain. At a significance level of .05, we found that the distribution of p-AKT stain scores for cancer was shifted to the right of adenoma (P < .000 I) and normal (P < .000 I) and for adenoma was shifted to the right of normal (P < .0001). AKT activation did not correlate with tumor stage (P = .28), lymph node metastasis (P = .45), lymphatic invasion (P = .46), or distant metastasis (P = .34). Conclusion: This study shows increasing activation of AKT during CRC progression. This finding suggests a role of p-AKT in colorectal carcinogenesis and provides a rationale for using p-AKT inhibitor API-2/triciribine, which is currently under clinical investigation for the treatment of CRC.
KW - Dysplasia
KW - Immunohistochemistry
KW - Tissue microarrays
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U2 - 10.3816/CCC.2007.n.034
DO - 10.3816/CCC.2007.n.034
M3 - Article
AN - SCOPUS:35348868179
SN - 1533-0028
VL - 6
SP - 652
EP - 656
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
IS - 9
ER -