Profiling of Hodgkin’s Lymphoma Cell Line L1236 and Germinal Center B Cells: Identification of Hodgkin’s Lymphoma-specific Genes

Abstract

The malignant cells of classical Hodgkin's lymphoma (cHL), Hodgkin and Reed-Sternberg (HRS) cells, appear to be derived from germinal center (GC) B cells in most cases of the disease. Apart from recent findings of constitutive activation of some transcription factors and autocrine stimulation by cytokine receptors, the mechanisms of malignant transformation in cHL still remain poorly understood. We performed a large scale gene expression study using serial analysis of gene expression (SAGE), comparing the cHL cell line L1236 and human GC B cells. Semiquantitative RT-PCR was used to confirm results from the SAGE and to analyze gene expression in 3 additional cHL cell lines. To investigate expression of some genes in cHL cases, we applied RT-PCR on microdissected HRS cells. In total, 464 genes showed a change in expression level of 5-fold or higher. For 12 genes (out of 177) identified as upregulated in L1236 cells, RT-PCR confirmed the SAGE results and also showed elevated expression in 3 other cHL cell lines. For 3 of the upregulated genes, expression by HRS cells in the tissue also was confirmed. Several of the differentially expressed genes may play a role in the pathogenesis of cHL because they represent potential oncogenes, such as rhoC, L-myc, and PTP4A, or transcription factors, such as ATF-5, ATBF1, and p21 SNFT. The genes that showed significantly deregulated expression in HRS cells should be helpful not only for the identification of genes involved in the pathogenesis of cHL but also for discovering potential prognostic markers or therapeutic targets.

PRL-3 facilitates angiogenesis and metastasis by increasing ERK phosphorylation and up-regulating the levels and activities of Rho-A/C in lung cancer

“…3 Subsequently, many scholars found that PRL-3 was highly expressed in many tumours, such as breast cancer, ovarian cancer, intestinal cancer, gliomas and stomach cancer, and was closely related to metastasis. 4-8 PRL-3 expression has also been reported in a Hodgkin's lymphoma cell line, 9 melanomas, liver, ovarian, breast and gastric cancers, where its presence seems to have an important role in the acquisition of metastatic potential of tumour cells. 10,11 Consistent with the role of PRL-3 over-expression in metastasis, its ectopic expression in different cell types is correlated with the induction of metastatic phenotypes, such as invasion and motility capabilities.…”

The role and target potential of protein tyrosine phosphatases in cancer

“…Elevated expression of PRL-2 in malignancies has been described in pediatric acute myeloid leukemia [35], Hodgkin's lymphoma cells [36], and prostate cancer [37]. PRL-1 overexpression in tumor tissues has been reported less frequently, although the phosphatase was expressed at higher levels in cell lines of melanoma [38] and pancreatic cancer [39].…”

Global gene expression profiling of formalin-fixed paraffin-embedded tumor samples: a comparison to snap-frozen material using oligonucleotide microarrays

“…For the dissection of an area of approximately 0.3 cm 2 of tumor tissue, 7-μm thick sections of frozen tissue were cut and stained with H&E essentially as described previously [22]. The tissue was dissected with a scalpel and transferred into a 0.5-ml tube.…”