Securin is overexpressed in breast cancer

Abstract

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.

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

“…12,36 Aneuploidy is a common feature of tumours overexpressing PTTG, and in breast cancer, the largest number of securin-positive cells was found in the tumours with the highest degree of pleomorphism. 6,16 We also found securin expression preferentially in pleomorphic melanoma cells with highly atypical or multiple nuclei. We studied the ploidy status in relation to hPTTG1 overexpression using a series of melanomas that had been karyotyped, and observed a significantly higher number of securinpositive cells in aneuploid cases.…”

“…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. Therefore, our results suggest that mechanisms other than angiogenesis are operating in hPTTG1-overexpressing melanomas.…”

“…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.…”

“…In tumours of the thyroid, securin is a prognostic marker for recurrence, 15 and in breast cancer, the extent of securin expression is associated with the presence of metastatic spread and lymph node invasion. 6,16 In cancer of the oesophagus and colorectum, high levels of hPTTG1 expression correlate with tumour invasiveness. 9 Recently, hPTTG1 has been identified as a key signature gene, with high expression predicting metastases in multiple tumour types.…”

Proliferation marker securin identifies favourable outcome in invasive ductal breast cancer

“…Evaluation of securin and Ki-67 immunoreactivity, and MAI Evaluation of securin and Ki-67 immunoreactivity, and MAI was performed on whole carcinoma sections based on the observed and reported (Ogbagabriel et al, 2005) focal nature of proliferation in tumour tissue. Securin and Ki-67 immunopositivities were determined by the fraction (%) of positively stained tumour cells and securin also by the intensity of staining (0, no staining; 1, weakly stained; 2, moderately stained; 3, strongly stained) at the areas of most pronounced staining, usually at the most cellular, infiltrating border of the tumour.…”