Establishment and phenotypic characterization of human U937 cells with inducible P210 BCR/ABL expression reveals upregulation of CEACAM1 (CD66a)

• Chronic myeloid leukemia (CML) is characterized by the expression of the P210 BCR/ABL fusion protein. The molecular mechanisms behind this oncogene-mediated hematological disease are, however, not fully understood. Here, we describe the establishment and phenotypic characterization of U937 cells in which P210 BCR/ABL can be conditionally expressed using tetracycline. The induction of BCR/ABL in the obtained clones resulted in a rapid phosphorylation of the STAT1, STAT3 and STAT5 molecules, consistent with the findings in other model systems. Phenotypic characterization of the clones revealed that BCR/ABL induces a slight decrease in the proliferation and viability, without a marked effect on cell cycle distribution, the rate of apoptosis or on cellular differentiation, as judged by several cell surface markers and capacity to reduce nitro blue tetrazolium. Interestingly, BCR/ABL was found to upregulate the expression of carcinoembryonic-related antigen (CEA)CAM1 (CD66a), which is a plasma membrane-linked glycoprotein belonging to the CEAs and involved in signal transduction and cellular adhesion. The expression of CEACAM1 was reversible upon imatinib treatment in BCR/ABL-expressing U937 cells as well as in BCR/ABL-positive K562 cells. The established cell lines may prove useful in further modeling and dissection of BCR/ABL-induced leukemogenesis.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

Antigens

CD/*metabolism

Antigens

Differentiation/*metabolism

Antineoplastic Agents/pharmacology

Apoptosis/drug effects

Carcinoembryonic Antigen/metabolism

Cell Adhesion Molecules

Cell Cycle/drug effects

Cell Differentiation/drug effects

DNA-Binding Proteins/metabolism

Fusion Proteins

bcr-abl/*genetics/metabolism

Humans

K562 Cells

Leukemia/*metabolism/pathology

*Milk Proteins

Phenotype

Piperazines/pharmacology

Protein-Tyrosine Kinases/antagonists & inhibitors

Pyrimidines/pharmacology

STAT1 Transcription Factor

STAT3 Transcription Factor

STAT5 Transcription Factor

Trans-Activators/metabolism

Transfection

U937 Cells

Up-Regulation

Publication and Content Type

ref (subject category)

art (subject category)