Expression of hpttg proto-oncogene in lymphoid neoplasias

Abstract

Pituitary tumor-transforming gene (pttg) is a distinct proto-oncogene which is expressed in certain normal tissues with high proliferation rate and in a variety of tumors. PTTG is the vertebrate analog of yeast securins Pds1 and Cut2 with a key role in the regulation of sister chromatid separation during mitosis. Impairment of PTTG regulated functions is expected to lead to chromosomal instability and aneuploidy. Human pttg (hpttg) is abundantly expressed in Jurkat T lymphoblastic lymphoma cells but not in normal peripheral blood leukocytes. To obtain additional data on the potential role of hpttg in lymphomagenesis we selected 150 cases of lymphoid tumors for the assessment of hpttg expression in tumor tissues. Immunohistochemical studies on formalin-fixed, paraffin-embedded tissues revealed hPTTG in 38.8% of B-cell lymphomas, 70.2% of Tcell lymphomas, and 73.1% of Hodgkin's lymphomas. Among B-cell lymphomas, the most frequently immunostained tumors were plasma cell tumors, diffuse large cell lymphomas, and follicle center cell lymphomas. In Hodgkin's disease, immunoreactivity was mainly noted in Reed-Sternberg cells. In conclusion, the frequent overexpression of hpttg in many histological subtypes of lymphoma suggests the involvement of this protooncogene in lymphomagenesis.

Pituitary tumour transforming gene (PTTG) induces genetic instability in thyroid cells

“…Increased expression of PTTG has been shown in many cancer cell lines and human tumours (including colorectal, breast, haematopoietic, and pituitary tumours) compared with normal tissues (Zhang et al, 1999;Heaney et al, 2000;Saez et al, 2002;Solbach et al, 2004). We recently reported significantly higher expression of PTTG in thyroid cancers compared with normal thyroid.…”

Anaphase-promoting complex-dependent proteolysis of cell cycle regulators and genomic instability of cancer cells

“…Securin is frequently overexpressed in hematopoietic neoplasms (Dominguez et al, 1998;Saez et al, 2002). Deletion of securin as well as blocked Figure 4 Regulation of sister chromatid separation by the APC.…”

Expression and possible role of hPTTG1/securin in cutaneous malignant melanoma

“…4 In normal tissues, securin expression is limited, in contrast to many human tumours, including pituitary adenomas, 5 lung and breast cancer, [5][6][7] colorectal cancer, 8 oesophageal cancer 9 and some lymphoid neoplasms. 10 The oncogenic mechanisms of hPTTG1 are still barely known, but there is accumulating evidence that the oncoprotein activity of securin is exerted at different levels, that is, by induction of angiogenesis through basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), 11 by prevention of separation of sister chromatids resulting in aneuploidy, 12 by activation of c-myc 13 and/or by specific interaction with p53, thereby blocking its transcriptional activity and inhibiting the ability of p53 to induce cell death. 14 In accordance with its oncogenic activities, hPTTG1 expression has been shown to have prognostic value.…”