Abstract
We investigated the Akt-mTOR pathway and effects of rapamycin using human colorectal cancer cell lines. LoVo and CaRI reduced proliferative activity in response to rapamycin in a dose-dependent manner. The phosphorylation of Akt and p70 S6K was prominent in these cells. Rapamycin quickly downregulated phospho-S6K but not phospho-Akt. Therefore, phospho-S6K is considered a good indicator of the activated Akt-mTOR pathway as well as rapamycin sensitivity in colorectal cancer cells. By immunohistochemical study, nearly 40% of adenomas and carcinomas of the colorectum exhibited either partial or whole positive staining for phospho-S6K, suggestive of rapamycin-sensitive lesions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibiotics, Antineoplastic / pharmacology
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Apoptosis / drug effects
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Blotting, Western
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Colorectal Neoplasms / metabolism
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Colorectal Neoplasms / pathology
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Dose-Response Relationship, Drug
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Flow Cytometry
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Humans
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Immunohistochemistry
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Ki-67 Antigen / analysis
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Phosphorylation / drug effects
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Protein Kinases / metabolism
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Proto-Oncogene Proteins c-akt / metabolism
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Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
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Signal Transduction / drug effects
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Sirolimus / pharmacology*
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TOR Serine-Threonine Kinases
Substances
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Antibiotics, Antineoplastic
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Ki-67 Antigen
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Protein Kinases
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MTOR protein, human
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Proto-Oncogene Proteins c-akt
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Ribosomal Protein S6 Kinases, 70-kDa
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TOR Serine-Threonine Kinases
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Sirolimus