The pituitary tumor transforming gene 1 (PTTG-1): An immunological target for multiple myeloma

Maurizio Chiriva-Internati¹^,2 , Raffaele Ferrari¹^,2 , Madhavi Prabhakar¹^,2 , Yuefei Yu¹^,2 , Luigi Baggoni⁴^,2 , Jorge Moreno³^,2 , Nicoletta Gagliano⁴^,2 , Nicola Portinaro⁶^,2 , Marjorie R Jenkins⁵ , Eldo E Frezza¹^,3 , Fred Hardwicke² , Nicholas D'Cunha² , W Martin Kast⁷ and Everardo Cobos¹^,2

¹Department of Microbiology and Immunology, Texas Tech University Health Sciences Center and Southwest Cancer Treatment and Research Center, Lubbock, TX, USA

²Division of Hematology and Oncology, Texas Tech University Health Sciences Center and Southwest Cancer Treatment and Research Center, Lubbock, TX, USA

³Division of Surgery, Texas Tech University Health Sciences Center and Southwest Texas Tech University Health Sciences Center and Southwest Cancer Treatment and Research Center, Lubbock, TX, USA

⁴Department of Human Morphology, University of Milan, Milan, Italy

⁵Department of Internal Medicine, Obstetrics & Gynecology and Laura W. Bush Institute for Women's Health and Center for Women's Health and Gender-Based Medicine, Texas Tech University Health Sciences Center, Amarillo, TX, USA

⁶Department of Pediatric Orthopedic Surgery, Istituto Clinico Humanitas, Rozzano, Milan, Italy

⁷Department of Molecular Microbiology & Immunology and Obstetrics & Gynecology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA

author email corresponding author email

Journal of Translational Medicine 2008, 6:15doi:10.1186/1479-5876-6-15


Published:	2 April 2008

Abstract

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.

Conclusion

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.