hpttg is over-expressed in pituitary adenomas and other primary epithelial neoplasias

Abstract

The role of oncogenes in pituitary tumorigenesis remains elusive since few genetic changes have been identi®ed so far in pituitary tumors. Pituitary tumortransforming gene (pttg) has been recently cloned from rat GH4 pituitary tumor cells. We have previously isolated and characterized hpttg from human thymus. In the present study, we analyse the expression of hpttg mRNA in a series of human pituitary adenomas. We show that hpttg is highly expressed in the majority of pituitary adenomas while only very low levels of mRNA can be detected in normal pituitary gland by Northern blot analysis. hPTTG protein was immunolocalized mainly in the cytoplasm of adenoma cells. Other common extra-cranial malignant tumors were also analysed by immunohistochemistry. Interestingly, strong hPTTG immunoreactivity was detected in most adenocarcinomas of mammary and pulmonary origins.

Pituitary tumor transforming gene interacts with Sp1 to modulate G1/S cell phase transition

“…Enhanced PTTG1 tumor abundance correlates with tumor development, size and malignancy (Saez et al, 1999;Honda et al, 2003). Our previous work showed that PTTG1À/À mice were viable (Wang et al, 2001), and are protected against Rb heterozygous tumor formation (Chesnokova et al, 2005), suggesting that PTTG1 knockdown could be a potential option for cancer treatment.…”

Chromosome instability in human lung cancers: possible underlying mechanisms and potential consequences in the pathogenesis

“…While ectopic expression of Securin, a sister-chromatid separation inhibitor, transforms NIH3T3 (Zou et al, 1999), up-regulation of Securin has been reported in some human tumors (Saez et al, 1999;Heaney et al, 2000). A human colorectal cancer cell line engineered to be securin deficient was shown to be abnormal in chromosome segregation, and to lose chromosomes at a high frequency (Jallepalli et al, 2001).…”

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

“…2,3 hPTTG1 is a proto-oncogene encoding for securin, a protein involved in several metabolic reactions, cellcycle progression, appropriate cell division and chromosome stability; upon overexpression, securin is involved in malignant transformation and tumorigenesis. 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.…”