Phosphorylation of ribosomal p70 S6 kinase and rapamycin sensitivity in human colorectal cancer.
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.
Nozawa
Hiroaki
H
Department of Surgical Oncology, University of Tokyo, 7-3-1 Hongo, Bunkyu-ku, Tokyo 113-8655, Japan. hiroanozawa-gi@umin.ac.jp <hiroanozawa-gi@umin.ac.jp>
Watanabe
Toshiaki
T
Nagawa
Hirokazu
H
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases
D000903:Antibiotics, Antineoplastic; D019394:Ki-67 Antigen; D011494:Protein Kinases; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus