Open AccessProto‐oncogene, Pim‐3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Bad‐mediated apoptosis
Author(s) -
Popivanova Boryana Konstantinova,
Li YingYi,
Zheng Huachuan,
Omura Kenji,
Fujii Chifumi,
Tsuneyama Koichi,
Mukaida Naofumi
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00390.x
Subject(s) - serine , oncogene , apoptosis , kinase , cancer research , threonine , cancer , colorectal cancer , akt3 , akt2 , biology , medicine , phosphorylation , microbiology and biotechnology , biochemistry , genetics , akt1 , cell cycle , pi3k/akt/mtor pathway
We previously observed that Pim‐3 with serine/threonine kinase activity, was aberrantly expressed in malignant lesions of endoderm‐derived organs, liver and pancreas. Because Pim‐3 protein was not detected in normal colon mucosal tissues, we evaluated Pim‐3 expression in malignant lesions of human colon, another endoderm‐derived organ. Pim‐3 was detected immunohistochemically in well‐differentiated (43/68 cases) and moderately differentiated (23/41 cases) but not poorly differentiated colon adenocarcinomas (0/5 cases). Moreover, Pim‐3 proteins were detected in adenoma (35/40 cases) and normal mucosa (26/111 cases), which are adjacent to adenocarcinoma. Pim‐3 was constitutively expressed in SW480 cells and the transfection with Pim‐3 short hairpin RNA promoted apoptosis. In the same cell line, a pro‐apoptotic molecule, Bad, was phosphorylated at Ser 112 and Ser 136 sites of phosphorylation that are representative of its inactive form. Ser 112 but not Ser 136 phosphorylation in this cell line was abrogated by Pim‐3 knockdown. Furthermore, in human colon cancer tissues, Pim‐3 co‐localized with Bad in all cases (9/9) and with phospho‐Ser 112 Bad in most cases (6/9). These observations suggest that Pim‐3 can inactivate Bad by phosphorylating its Ser 112 in human colon cancer cells and thus may prevent apoptosis and promote progression of human colon cancer. ( Cancer Sci 2007; 98: 321–328)