Expression of the ALK Tyrosine Kinase Gene in Neuroblastoma

Abstract

ALK (anaplastic lymphoma kinase) is a tyrosine kinase receptor, expressed as part of the chimeric NPM-ALK protein, in anaplastic large cell lymphomas (ALCLs) exhibiting the t(2;5)(p23;q35) translocation. As a result of this translocation, the NPM (nucleophosmin) gene is fused to the portion of the ALK gene encoding its intracytoplasmic segment. In normal mouse tissues, mRNA encoding the Alk receptor has been found only in neural cells, suggesting involvement of this receptor in the development of the nervous system. The purpose of the present study was to examine the presence of ALK transcripts and protein in normal human tissues and a variety of cell lines and human tumors. Emphasis was placed on neuroblastomas because other tyrosine kinase receptors are expressed in human neuroblastomas. Fifty-six cell lines, including 29 lines of neural origin, and lymphoid and nonlymphoid tissue specimens, including 24 neuroblastomas, were investigated for ALK expression, using reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry. The results confirmed that mRNA encoding ALK protein was not detectable in any normal or neoplastic hematopoietic tissue tested, except for t(2;5)-positive ALCL. The salient finding was that 13 of the 29 cell lines of neural origin and 22 of 24 neuroblastomas were found to express ALK transcripts and ALK protein. However, no correlation was evident between any known prognostic factors and the level of ALK expression.

Midkine Lacking Its Last 40 Amino Acids Acts on Endothelial and Neuroblastoma Tumor Cells and Inhibits Tumor Development

“…Five out of 8 cell lines exhibited high ALK expression, whereas 3 expressed only low levels. These results are consistent with previous reports which showed that full-length ALK is detected in almost half of the cell lines derived from neuroblastomas (33,34). We were unable to show that these patterns of expression were associated with ALK amplification and that there was an association between ALK and N-myc amplification.…”

Renal cell carcinoma with novel VCL–ALK fusion: new representative of ALK-associated tumor spectrum

“…After a brief washing and subsequent incubation with the goatanti-mouse horseradish peroxidase-conjugated secondary antibody (Santa Cruz Biotechnology), the blots were developed by enhanced chemiluminescence reaction (ECL Detection reagents; GE Healthcare Global, Piscataway, NJ, USA). The human neuroblastoma cell line IMR32 30 with a recognized full-length ALK expression and normal kidney tissue were used as controls of ALK and VCL expression, respectively. Mouse monoclonal antib-actin primary antibody (Sigma-Aldrich) was used as the protein-loading control.…”

Anaplastic lymphoma kinase is expressed in different subtypes of human breast cancer

“…However, ALK was originally discovered when it was found that the chimeric N-terminal nucleophosmin (NPM) domain/cytoplasmic (catalytic) ALK domain fusion protein (NPM-ALK) is the oncoprotein underlying the pathogenesis of anaplastic large cell lymphomas (ALCL) [5,6]. NPM-ALK results from the (2;5) (p23;q35) chromosomal translocation, however, other translocations also lead to constitutive activation of ALK and other malignancies and furthermore, wild-type ALK has been postulated to be involved in the pathogenesis of rhabdomyosarcomas [7], neuroblastoma and neuroectodermal tumors [8,9], glioblastomas [10], and melanomas [11].…”