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

Winnepenninckx, Véronique; Dębiec‐Rychter, Maria; Beliën, Jeroen A.M.; Fiten, Pierre; Michiels, Stefan; Lazar, Vladimir; Opdenakker, Ghislain; Meijer, Gerrit A.; Spatz, Alan

doi:10.1038/modpathol.3800627

Cited by 24 publications

(23 citation statements)

References 37 publications

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“…We show for the first time that the effect of CDC23 knockdown on cellular proliferation could be reversed by the simultaneous knockdown of cyclin B1 and securin. This finding suggests that the effect of CDC23 is mediated, at least in part, by cyclin B1 and securin which is consistent with the role of these two proteins in cancer progression (Bowers & Boylan 2004, Borlak et al 2005, Winnepenninckx et al 2006, Salehi et al 2008.…”

Section: Discussionsupporting

confidence: 70%

CDC23 regulates cancer cell phenotype and is overexpressed in papillary thyroid cancer

Zhang¹,

Rahbari²,

He³

et al. 2011

Endocrine-Related Cancer

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Cancer gender disparities have been observed for a variety of human malignancies. Thyroid cancer is one such example where there is a dramatic difference in the incidence, aggressiveness, and death rate by gender. The molecular basis for gender disparity is poorly understood. To address this, we performed genome-wide gene expression profiling in matched papillary thyroid cancer (PTC) samples and identified nine candidate genes differentially expressed by gender. One of these genes was CDC23 that was upregulated in PTC in men compared with women. Because the function and expression of CDC23 is unknown in eukaryotic cells, we further characterized the expression of CDC23 in normal, hyperplastic, and PTC tissue samples. We found CDC23 was overexpressed in PTC and absent in normal and hyperplastic thyroid tissue. In thyroid cancer cells, functional knockdown of CDC23 resulted in an increase in the number of cells in both the S and G 2 M phases of the cell cycle, and an inhibition of cellular proliferation, tumor spheroid formation, and anchorage-independent growth. Cellular arrest in both S and G 2 M phases was associated with significant cyclin B1 and securin protein accumulation after CDC23 knockdown. Moreover, the effect of CDC23 on cellular proliferation and cell cycle progression was reversed on triple knockdown studies of CDC23, cyclin B1, and securin. Our data taken together suggests CDC23 has important biologic effects on cell proliferation and cell cycle progression. The effect of CDC23 on cellular proliferation and cell cycle progression is mediated, at least in part, by cyclin B1 and securin protein levels. Therefore, we propose that CDC23 is a critical regulator of cell cycle and cell growth, and may be involved in thyroid cancer initiation and progression, and may explain the different tumor biology observed by gender.

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Section: Discussionsupporting

confidence: 70%

CDC23 regulates cancer cell phenotype and is overexpressed in papillary thyroid cancer

Zhang¹,

Rahbari²,

He³

et al. 2011

Endocrine-Related Cancer

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“…However, the respective roles of the biological characteristics of micrometastatic tumor cells and SLN immune response remain largely unknown. In a genomics study of primary melanomas, we found that primary melanomas with metastatic evolution were characterized by a dysregulation in key pathways driving replication, including the replication origins firing (ROF) system and survivin gene involved in chromatid separations (37,38). We found no difference in expression signature between primary melanomas and metastases, illustrating once more that the genetic machinery for melanoma metastases evolution is acquired early in melanoma development.…”

Section: Discussionmentioning

confidence: 78%

Long-Term Protective Effect of Mature DC-LAMP+ Dendritic Cell Accumulation in Sentinel Lymph Nodes Containing Micrometastatic Melanoma

Elliott

Scolyer

Suciu

et al. 2007

Clinical Cancer Research

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Purpose: In a previous immunohistochemical study of dendritic cells (DC) in sentinel lymph nodes (SLN) draining regressing melanomas, we found that the accumulation of mature DC-LAMP + DCs in SLNs was associated with local expansion of antigen-specific memory effector CTLs and the absence of metastasis in downstream lymph nodes. The aim of this study was to investigate the prognostic importance of the maximal density of mature DCs in SLNs. Experimental Design: A total of 458 consecutive patients with micrometastatic melanoma within SLNs were eligible for analysis. The maximal density of mature DC-LAMP + DCs was evaluated by three independent observers and categorized into three classes (<100, 100 to <200, and z200/mm 2 ). Results: There was excellent interobserver reproducibility for maximum density of mature DC-LAMP + DC scores (j score = 0.82). There were differences in the maximal density scores and staining intensity according to the treating melanoma center (P < 0.001). The higher the mature DC density in the SLN is, the longer is the duration of survival [P = 0.047; hazard ratio, 0.70; 95% confidence interval, 0.50-1.00]. Adjusted by thickness and ulceration, the prognostic importance of DC density was lower (P = 0.36).Conclusion: This study is the first to report the prognostic value of DC-LAMP + DC counts in SLNs containing metastatic melanoma. Patients with a high density of mature DCs (z200/mm 2 ) have the lowest risk of death. It also provides evidence that a lack of maturation in the SLNs is important in biological facilitation of melanoma progression.

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“…In colorectal cancers patients, such instability correlates with higher tumor grade, indicating that PTTG and genetic instability may be linked in these tumors (Kim et al 2007a). PTTG expression also correlates with aneuploidy in melanomas (Winnepenninckx et al 2006) and in follicular as well as papillary thyroid carcinomas . In vitro transfection of colorectal (Kim et al 2007a) and follicular thyroid as well as of HeLa and A549 cells (Mu et al 2003) has been shown to induce both genetic instability and aneuploidy.…”

Section: Genetic Instabilitymentioning

confidence: 93%

“…In a series of 29 nodular and 29 superficial spreading melanomas, PTTG correlated with aneuploidy as well as the nodular type (Winnepenninckx et al 2006). The expression of PTTG mRNA in multiple myeloma (NZ33) has been shown to be significantly higher than in normal controls .…”

Section: Uterusmentioning

confidence: 99%

“…Other cancers PTTG expression has been demonstrated in a variety of tumors and cancer cell lines (Dominguez et al 1998, McCabe & Gittoes 1999, Heaney et al 2000, Saez et al 2002, Shibata et al 2002, Honda et al 2003, Ai et al 2004, Grutzmann et al 2004, Wen et al 2004, Zhou et al 2005, Fujii et al 2006, Rehfeld et al 2006, Sato et al 2006, Su et al 2006, Winnepenninckx et al 2006, Kim et al 2007a. Microarray analysis of 14 pancreatic ductal carcinomas and pancreatic carcinoma cell lines identified PTTG1 as one of the differentially expressed genes (Grutzmann et al 2004).…”

Section: Uterusmentioning

confidence: 99%

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Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update

Salehi

Kovács²,

Scheithauer³

et al. 2008

Endocrine Related Cancer

119

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Pituitary tumor-transforming gene (PTTG) was only recently discovered. Its overexpression occurs in a wide variety of endocrine and non-endocrine tumors, including ones of pituitary, thyroid, ovary, breast, prostate, lung, esophagus, colon, and the central nervous system. It affects tumor invasiveness and recurrence in several systems, functions as a securin during cell cycle progression, and inhibits premature sister chromatid separation. PTTG is involved in multiple cellular pathways, including proliferation, DNA repair, transformation, angiogenesis induction, invasion, and the induction of genetic instability. In thyroid carcinomas, PTTG expression is a marker of invasiveness. PTTG is overexpressed in most pituitary adenomas, where it appears to correlate with recurrence and angiogenesis. Increasing evidence also points to the role of PTTG in endocrine organ development. For example, PTTG knockout mice show defective pancreatic b-cell proliferation. Herein, we review the current knowledge regarding PTTG-mediated pathways based on evidence from in vivo and in vitro studies as well as knockout mice models. We also summarize the issue of PTTG expression and its correlation with clinicopathologic parameters in patients with neoplasms, particularly of endocrine organs. In addition, we discuss in vitro and in vivo therapeutic models targeting PTTG overexpression.

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

Cited by 24 publications

References 37 publications

CDC23 regulates cancer cell phenotype and is overexpressed in papillary thyroid cancer

CDC23 regulates cancer cell phenotype and is overexpressed in papillary thyroid cancer

Long-Term Protective Effect of Mature DC-LAMP+ Dendritic Cell Accumulation in Sentinel Lymph Nodes Containing Micrometastatic Melanoma

Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update

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