Activation of the serine/threonine protein kinase AKT during the progression of colorectal neoplasia

Ozlen Saglam, Christopher R. Garrett, David Boulware, Zena Sayegh, David Shibata, Mokenge Malafa, Timothy Yeatman, Jin Q. Cheng, Said Sebti, Domenico Coppola

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)652-656
Number of pages5
JournalClinical Colorectal Cancer
Volume6
Issue number9
DOIs
StatePublished - Jan 1 2007

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Protein-Serine-Threonine Kinases
Adenoma
Colorectal Neoplasms
triciribine
Carcinoma
Neoplasms
Carcinogenesis
Mucous Membrane
Coloring Agents
Neoplasm Metastasis
Avidin
Biotin
Adenocarcinoma
Lymph Nodes
Cell Proliferation
Apoptosis
Antibodies

All Science Journal Classification (ASJC) codes

  • Oncology
  • Gastroenterology

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Activation of the serine/threonine protein kinase AKT during the progression of colorectal neoplasia. / Saglam, Ozlen; Garrett, Christopher R.; Boulware, David; Sayegh, Zena; Shibata, David; Malafa, Mokenge; Yeatman, Timothy; Cheng, Jin Q.; Sebti, Said; Coppola, Domenico.

In: Clinical Colorectal Cancer, Vol. 6, No. 9, 01.01.2007, p. 652-656.

Research output: Contribution to journalArticle

Saglam, O, Garrett, CR, Boulware, D, Sayegh, Z, Shibata, D, Malafa, M, Yeatman, T, Cheng, JQ, Sebti, S & Coppola, D 2007, 'Activation of the serine/threonine protein kinase AKT during the progression of colorectal neoplasia', Clinical Colorectal Cancer, vol. 6, no. 9, pp. 652-656. https://doi.org/10.3816/CCC.2007.n.034
Saglam, Ozlen ; Garrett, Christopher R. ; Boulware, David ; Sayegh, Zena ; Shibata, David ; Malafa, Mokenge ; Yeatman, Timothy ; Cheng, Jin Q. ; Sebti, Said ; Coppola, Domenico. / Activation of the serine/threonine protein kinase AKT during the progression of colorectal neoplasia. In: Clinical Colorectal Cancer. 2007 ; Vol. 6, No. 9. pp. 652-656.
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abstract = "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.",
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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 - 2007/1/1

Y1 - 2007/1/1

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.

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