The pituitary tumor transforming gene 1 (PTTG-1): an immunological target for multiple myeloma.
BACKGROUND
Multiple 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.


METHODS
We 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.


RESULTS
We 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.


CONCLUSIONS
We 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.
Chiriva-Internati
Maurizio
M
Department of Microbiology and Immunology, Texas Tech University Health Sciences Center and Southwest Cancer Treatment and Research Center, Lubbock, TX, USA. maurizio.chiriva@ttuhsc.edu
Ferrari
Raffaele
R
Prabhakar
Madhavi
M
Yu
Yuefei
Y
Baggoni
Luigi
L
Moreno
Jorge
J
Gagliano
Nicoletta
N
Portinaro
Nicola
N
Jenkins
Marjorie R
MR
Frezza
Eldo E
EE
Hardwicke
Fred
F
D'Cunha
Nicholas
N
Kast
Wmartin
W
Cobos
Everardo
E
D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008565:Membrane Proteins / Q000378:metabolism; D009101:Multiple Myeloma / Q000235:genetics* / Q000276:immunology*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D010957:Plasmids; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D064249:Securin; D015534:Trans-Activators
D007074:Immunoglobulin G; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D064249:Securin; D015534:Trans-Activators; C578002:pituitary tumor-transforming protein 1, human