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PTEN, but not SHIP and SHIP2, suppresses the PI3K/Akt pathway and induces growth inhibition and apoptosis of myeloma cells.
Oncogene. 2002 Aug 08; 21(34):5289-300.O

Abstract

Expression of PTEN tumor suppressor gene has been known to dephosphorylate the phosphatidylinositol 3' kinase (PI3K) products on the 3 prime inositol ring, resulting in reduced Akt activation. Loss of PTEN expression in OPM2 and delta47 human myeloma lines led to high Akt activity toward insulin-like growth factor I (IGF-I). In contrast, mouse plasma cell tumor (PCT) lines, expressing wild type PTEN, did not respond to IGF-I for Akt activation. We demonstrated here that endogenous PTEN played a negative role in controlling Akt activity in both mouse PCT and NIH3T3 fibroblast lines by using anti-sense oligonucleotides against PTEN. To determine the role of src-homology 2-containing inositol 5' phosphatase (SHIP) in regulating the PI3K/Akt pathway, we manipulated its expression by down-regulation and overexpression in myeloma, PCT and NIH3T3 lines and analysed Akt activation. Our results showed that SHIP, unlike PTEN, did not affect Akt activity in all systems analysed, despite its ability to dephosphorylate a PI3K product. Although SHIP2 expression resulted in suppression of interleukin-6-mediated mitogen-activated protein kinase activation, expression of SHIP and SHIP2 in a PTEN-null myeloma line did not suppress Akt activity. Biologically, expression of only PTEN, but not SHIP and SHIP2, resulted in growth inhibition and increased apoptosis in OPM2 myeloma line. Together, our results have established the role of PTEN, but not SHIP and SHIP2, in negatively regulating the PI3K/Akt cascade and in myeloma leukemogenesis.

Authors+Show Affiliations

Lomabardi Cancer Center, Georgetown University Medical Center, Washington, District of Colombia 20007, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12149650

Citation

Choi, Yong, et al. "PTEN, but Not SHIP and SHIP2, Suppresses the PI3K/Akt Pathway and Induces Growth Inhibition and Apoptosis of Myeloma Cells." Oncogene, vol. 21, no. 34, 2002, pp. 5289-300.
Choi Y, Zhang J, Murga C, et al. PTEN, but not SHIP and SHIP2, suppresses the PI3K/Akt pathway and induces growth inhibition and apoptosis of myeloma cells. Oncogene. 2002;21(34):5289-300.
Choi, Y., Zhang, J., Murga, C., Yu, H., Koller, E., Monia, B. P., Gutkind, J. S., & Li, W. (2002). PTEN, but not SHIP and SHIP2, suppresses the PI3K/Akt pathway and induces growth inhibition and apoptosis of myeloma cells. Oncogene, 21(34), 5289-300.
Choi Y, et al. PTEN, but Not SHIP and SHIP2, Suppresses the PI3K/Akt Pathway and Induces Growth Inhibition and Apoptosis of Myeloma Cells. Oncogene. 2002 Aug 8;21(34):5289-300. PubMed PMID: 12149650.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PTEN, but not SHIP and SHIP2, suppresses the PI3K/Akt pathway and induces growth inhibition and apoptosis of myeloma cells. AU - Choi,Yong, AU - Zhang,Jie, AU - Murga,Cristina, AU - Yu,Hong, AU - Koller,Erich, AU - Monia,Brett P, AU - Gutkind,J Silvio, AU - Li,Weiqun, PY - 2002/02/26/received PY - 2002/05/03/revised PY - 2002/05/07/accepted PY - 2002/8/1/pubmed PY - 2002/8/31/medline PY - 2002/8/1/entrez SP - 5289 EP - 300 JF - Oncogene JO - Oncogene VL - 21 IS - 34 N2 - Expression of PTEN tumor suppressor gene has been known to dephosphorylate the phosphatidylinositol 3' kinase (PI3K) products on the 3 prime inositol ring, resulting in reduced Akt activation. Loss of PTEN expression in OPM2 and delta47 human myeloma lines led to high Akt activity toward insulin-like growth factor I (IGF-I). In contrast, mouse plasma cell tumor (PCT) lines, expressing wild type PTEN, did not respond to IGF-I for Akt activation. We demonstrated here that endogenous PTEN played a negative role in controlling Akt activity in both mouse PCT and NIH3T3 fibroblast lines by using anti-sense oligonucleotides against PTEN. To determine the role of src-homology 2-containing inositol 5' phosphatase (SHIP) in regulating the PI3K/Akt pathway, we manipulated its expression by down-regulation and overexpression in myeloma, PCT and NIH3T3 lines and analysed Akt activation. Our results showed that SHIP, unlike PTEN, did not affect Akt activity in all systems analysed, despite its ability to dephosphorylate a PI3K product. Although SHIP2 expression resulted in suppression of interleukin-6-mediated mitogen-activated protein kinase activation, expression of SHIP and SHIP2 in a PTEN-null myeloma line did not suppress Akt activity. Biologically, expression of only PTEN, but not SHIP and SHIP2, resulted in growth inhibition and increased apoptosis in OPM2 myeloma line. Together, our results have established the role of PTEN, but not SHIP and SHIP2, in negatively regulating the PI3K/Akt cascade and in myeloma leukemogenesis. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/12149650/PTEN_but_not_SHIP_and_SHIP2_suppresses_the_PI3K/Akt_pathway_and_induces_growth_inhibition_and_apoptosis_of_myeloma_cells_ L2 - https://doi.org/10.1038/sj.onc.1205650 DB - PRIME DP - Unbound Medicine ER -