PMID- 10220386
OWN - NLM
STAT- MEDLINE
DCOM- 19990610
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 9
DP  - 1999 Apr 27
TI  - Dedifferentiation of adenocarcinomas by activation of phosphatidylinositol 
      3-kinase.
PG  - 4874-9
AB  - Signet ring cell carcinoma is a malignant type of poorly differentiated 
      adenocarcinomas in stomach, which is characterized by the occasional presence of 
      signet ring-like cancer cells. We found that expression of constitutively active 
      phosphatidylinositol 3-kinase (PI 3-kinase) in well differentiated adenocarcinoma 
      cell lines induced the loss of cell-cell contact and some of the cells changed 
      their shapes to signet ring cell-like, characterized by appearance of mucus 
      droplets in the cytoplasm with well developed endplasmic reticulum and Golgi 
      complexes. The active PI 3-kinase-expressing cells formed poorly differentiated 
      tumors in nude mice, which were clearly different from those of the original cell 
      lines. The PI 3-kinase activities detected in anti-phosphotyrosine 
      immunoprecipitates were higher in several signet ring cell carcinoma-derived cell 
      lines than in other adenocarcinoma cell lines. In addition, PI 3-kinase was found 
      to be associated with a 200-kDa protein phosphorylated in tyrosine in 4 of 6 
      signet ring cells but not in other cell lines, suggesting that PI 3-kinase is 
      possibly activated in these cells by binding to the 200-kDa protein. The 200-kDa 
      protein-PI 3-kinase complex was exclusively fractionated in the membrane 
      fractions. The specific activity of the PI 3-kinase immunoprecipitated with 
      anti-phosphotyrosine antibody was approximately 3-fold higher than that with 
      anti-PI 3-kinase antibody. These results suggest that PI 3-kinase in signet ring 
      cell carcinoma is recruited to the membrane and activated by the binding to the 
      200-kDa protein.
FAU - Kobayashi, M
AU  - Kobayashi M
AD  - Laboratory of Biological Chemistry, Department of Applied Biological Chemistry, 
      Faculty of Agricultural and Life Science, University of Tokyo, Yayoi 1-1-1, 
      Bunkyo-ku, Tokyo 113-8657, Japan.
FAU - Nagata, S
AU  - Nagata S
FAU - Iwasaki, T
AU  - Iwasaki T
FAU - Yanagihara, K
AU  - Yanagihara K
FAU - Saitoh, I
AU  - Saitoh I
FAU - Karouji, Y
AU  - Karouji Y
FAU - Ihara, S
AU  - Ihara S
FAU - Fukui, Y
AU  - Fukui Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Adenocarcinoma/metabolism/*pathology
MH  - Animals
MH  - Cell Differentiation
MH  - Enzyme Activation
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Signal Transduction
MH  - Stomach Neoplasms/metabolism/*pathology
MH  - Tumor Cells, Cultured
PMC - PMC21784
EDAT- 1999/04/29 00:00
MHDA- 1999/04/29 00:01
PMCR- 1999/10/27
CRDT- 1999/04/29 00:00
PHST- 1999/04/29 00:00 [pubmed]
PHST- 1999/04/29 00:01 [medline]
PHST- 1999/04/29 00:00 [entrez]
PHST- 1999/10/27 00:00 [pmc-release]
AID - 0645 [pii]
AID - 10.1073/pnas.96.9.4874 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):4874-9. doi: 10.1073/pnas.96.9.4874.