Abstract
BackgroundMultiple Myeloma is a cancer of B plasma cells, which produce non-specific antibodies and proliferate uncontrolled. Due to the potential relapse and non-specificity of current treatments, immunotherapy promises to be more specific and may induce long-term immunity in patients. The pituitary tumor transforming gene 1 (PTTG-1) has been shown to be a novel oncogene, expressed in the testis, thymus, colon, lung and placenta (undetectable in most other tissues). Furthermore, it is over expressed in many tumors such as the pituitary adenoma, breast, gastrointestinal cancers, leukemia, lymphoma, and lung cancer and it seems to be associated with tumorigenesis, angiogenesis and cancer progression. The purpose was to investigate the presence/rate of expression of PTTG-1 in multiple myeloma patients.MethodsWe analyzed the PTTG-1 expression at the transcriptional and the protein level, by PCR, immunocytochemical methods, Dot-blot and ELISA performed on patient's sera in 19 multiple myeloma patients, 6 different multiple myeloma cell lines and in normal human tissue.ResultsWe did not find PTTG-1 presence in the normal human tissue panel, but PTTG-1 mRNA was detectable in 12 of the 19 patients, giving evidence of a 63% rate of expression (data confirmed by ELISA). Four of the 6 investigated cell lines (66.6%) were positive for PTTG-1. Investigations of protein expression gave evidence of 26.3% cytoplasmic expression and 16% surface expression in the plasma cells of multiple myeloma patients. Protein presence was also confirmed by Dot-blot in both cell lines and patients.ConclusionWe established PTTG-1's presence at both the transcriptional and protein levels. These data suggest that PTTG-1 is aberrantly expressed in multiple myeloma plasma cells, is highly immunogenic and is a suitable target for immunotherapy of multiple myeloma.
Highlights
Multiple Myeloma is a cancer of B plasma cells, which produce non-specific antibodies and proliferate uncontrolled
We wanted to investigate a panel of normal human tissues constituted by brain, breast, colon, heart, kidney, liver, lung, ovary, pancreas, skeletal muscle, spleen, stomach and bone marrow to evaluate the presence of pituitary tumor transforming gene 1 (PTTG-1) at both the transcriptional and the protein levels
Our investigation of the 13 above mentioned human normal tissues gave no evidence of positive band signals for PTTG-1 (Fig. 2A) by PCR
Summary
Multiple Myeloma is a cancer of B plasma cells, which produce non-specific antibodies and proliferate uncontrolled. The pituitary tumor transforming gene 1 (PTTG-1) has been shown to be a novel oncogene, expressed in the testis, thymus, colon, lung and placenta (undetectable in most other tissues). It is over expressed in many tumors such as the pituitary adenoma, breast, gastrointestinal cancers, leukemia, lymphoma, and lung cancer and it seems to be associated with tumorigenesis, angiogenesis and cancer progression. Multiple myeloma (MM) is a malignancy of B plasma cells (PCs). They accumulate in the bone marrow (BM) causing bone destruction, BM failure [1] and interfere with the normal PC activity by generating an abnormal, non-functional and non-specific immunoglobulin (M protein) [2]. Treatment for MM is currently based on high doses of chemotherapy, radiotherapy and autologous stem cell rescue, but death is the ultimate outcome
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