Expression of the PTTG1 oncogene is associated with aggressive clear cell renal cell carcinoma.
The pituitary tumor transforming gene (PTTG1) is a recently discovered oncogene implicated in malignant progression of both endocrine and nonendocrine malignancies. Clear cell renal cell carcinoma (ccRCC) is cytogenetically characterized by chromosome 3p deletions that harbor the ccRCC-related von Hippel-Lindau, PBRM1, BAP1, and SETD2 tumor suppressor genes, along with chromosome 5q amplifications where the significance has been unclear. PTTG1 localizes to the chromosome 5q region where amplifications occur in ccRCC. In this study, we report a functional role for PTTG1 in ccRCC tumorigenesis. PTTG1 was amplified in ccRCC, overexpressed in tumor tissue, and associated with high-grade tumor cells and poor patient prognosis. In preclinical models, PTTG1 ablation reduced tumorigenesis and invasion. An analysis of gene expression affected by PTTG1 indicated an association with invasive and metastatic disease. PTTG1-dependent expression of the RhoGEF proto-oncogene ECT2 was observed in a number of ccRCC cell lines. Moreover, ECT2 expression correlated with PTTG1 expression and poor clinical features. Together, our findings reveal features of PTTG1 that are consistent with its identification of an oncogene amplified on chromsome 5q in ccRCC, where it may offer a novel therapeutic target of pathologic significance in this disease.
Laboratories of Cancer Genetics, Cytogenetics, and Computational Biology, Van Andel Research Institute; Department of Urology, Spectrum Health Hospital, Grand Rapids, MI 49503, USA.
Bill
B
Wondergem
Zhongfa
Z
Zhang
Dachuan
D
Huang
Choon Kiat
CK
Ong
Julie
J
Koeman
David Van't
DV
Hof
David
D
Petillo
Aikseng
A
Ooi
John
J
Anema
Brian
B
Lane
Richard J
RJ
Kahnoski
Kyle A
KA
Furge
Bin Tean
BT
Teh
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002895:Chromosomes, Human, Pair 5; D016000:Cluster Analysis; D005784:Gene Amplification; D018628:Gene Dosage; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D064249:Securin; D014183:Transplantation, Heterologous
C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human