Expression of pituitary-tumour transforming gene in colorectal tumours

Heaney, Anthony P.; Singson, Regina; McCabe, Chris; Nelson, Viera; Nakashima, Masahiro; Melmed, Shlomo

doi:10.1016/s0140-6736(99)10238-1

Cited by 207 publications

(188 citation statements)

References 22 publications

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“…18 These data are in line with studies on breast, colorectal and thyroid carcinomas in which overexpression of PTTG is associated with early recurrence, or metastatic spread and thus with a poor prognosis. 8,15,16 In normal cells, the securin protein is expressed in a cell-cycle-dependent manner and regulates sister chromatid separation to opposite poles of the cell during anaphase. 4 Following cytoplasmic to nuclear translocation, it peaks in the G2/M phase and subsequently is ubiquitinated and degraded in the proteasome.…”

Section: Discussionmentioning

confidence: 99%

“…39 Ishikawa et al 11 showed that hPTTG1 induces an angiogenic phenotype in both in vitro and in vivo angiogenesis models. Highly vascularised colorectal cancers express high levels of securin, 8 and in breast carcinoma, securin-mediated angiogenesis may contribute to an invasive breast tumour phenotype. 6 We could not confirm these results as we did not find a correlation between securin expression, on the one hand, and bFGF immunoreactivity or microvessel density, on the other.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

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

et al. 2006

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Human pituitary tumour-transforming gene 1 or hPTTG1 is a proto-oncogene that codes for securin, a protein involved in sister chromatid separation. Based on previous microarray data, we studied the expression of hPTTG1/securin in melanocytic lesions. In contrast to nevi and radial growth phase melanomas, securin was expressed by scattered cells in the vertical growth phase, suggesting a role in tumour progression. In a series of 29 nodular and 29 superficial spreading melanomas, matched for all histological prognostic parameters, securin expression was significantly correlated with the nodular subtype (P ¼ 0.018) and not related to thickness. In other cancers, hPTTG1 is involved in various oncogenic pathways, including induction of neovascularisation and aneuploidy, and inhibition of p53 activity. We found coexpression of securin with wildtype p53 in the same neoplastic cells in a minority of melanomas. Expression of securin was significantly correlated with the extent of aneuploidy but not with basic fibroblast growth factor immunoreactivity or microvessel density. DNA cytometry revealed that nuclei-overexpressing securin frequently showed tetraploidy or aneuploidy. Our data show that hPTTG1 is frequently overexpressed in nodular melanoma, and suggest that hPTTG1 may act as an oncogene in the vertical growth phase, either by inhibiting anaphase, thereby causing aneuploidy and genomic instability, or by modulating the function of p53, thereby impairing apoptosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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

et al. 2006

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“…14 In addition to its actions on cell-cycle regulation, securinmediated angiogenesis may provide a further mechanism whereby securin abundance contributes to an invasive breast tumor phenotype.…”

Section: Securin Overexpression In Breast Cancermentioning

confidence: 99%

“…7 Securin overexpression leads to aneuploidy, 8,9 causes in vitro transformation, and tumor formation in vivo, regulates bFGF secretion and induces angiogenesis. 10,11 Securin is expressed at low levels in normal tissues, but is abundantly expressed in human pituitary, 12 thyroid 13 and colorectal tumors, 14 where highest securin mRNA expression was observed in invasive and metastatic cancers.…”

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Securin is overexpressed in breast cancer

et al. 2005

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Securin regulates sister chromatid separation during mitosis, induces bFGF-mediated angiogenesis, and securin overexpression causes in vitro transformation and in vivo tumor formation in nude mice. As estrogen administration to oophorectomized rats increased pituitary securin expression, we used immunohistochemistry to examine securin and estrogen receptor alpha (ER-a) expression in 90 breast tumors and 18 normal breast tissues. Breast tumor securin and ER-a expression were quantitated by image analysis and expressed as fold difference relative to securin expression in normal breast tissue. Low cytoplasmic securin expression was seen in the normal breast epithelium, whereas abundant cytoplasmic and nuclear securin expression was demonstrated in all 90 breast tumors. Highest securin expression was seen in brain metastatic breast tumors (4.3-fold, Po0.01), cells derived from metastatic breast cancers (6.5-fold, Po0.001), and in invasive ductal carcinoma (mean7s.e.: 3.8-fold, Po0.001). Highly pleomorphic (4.1-fold) or highly proliferative breast tumors (1.6-fold) exhibited high immunohistochemical securin expression compared to low-grade breast tumors (Po0.05). Northern blot analysis in 12 of the breast tumors confirmed the immunohistochemical findings demonstrating increased securin mRNA expression compared to normal breast mucosa (2.5-fold, P ¼ 0.03), with highest securin evident in invasive (3.5-fold) vs noninvasive tumors (1.9-fold, P ¼ 0.03). In addition, some tumors that exhibited high securin expression also expressed high ER-a levels (Po0.0001). These results demonstrate that the estrogen-induced transforming gene, securin is abundantly expressed in breast carcinoma, and is associated with the presence of metastatic spread, and lymph node invasion. We propose immunohistochemical tumor securin expression as a potential invasive marker, and novel therapeutic target in breast cancer. Modern Pathology (2005) 18, 985-990.

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Anaphase‐Promoting Complex (APC,APC/C, Cyclosome)

Peters

2002

Wiley Encyclopedia of Molecular Medicine

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Expression of pituitary-tumour transforming gene in colorectal tumours

Cited by 207 publications

References 22 publications

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

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

Securin is overexpressed in breast cancer

Anaphase‐Promoting Complex (APC,APC/C, Cyclosome)

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