Abnormal cell cycle regulation in primary human uveal melanoma cultures

Pardo, María; Piñeiro, Antonio; Fuente, María de la; García, Ángel; Prabhakar, S.; Zitzmann, Nicole; Dwek, Raymond A.; Sánchez-Salorio, Manuel; Domı́nguez, Fernando; Capeáns, C.

doi:10.1002/jcb.20230

Cited by 25 publications

(31 citation statements)

References 45 publications

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“…These data are in accord with literature reports of negative or weak expression of cyclin D1 in benign melanocytic lesions and high levels in cutaneous melanomas [22][23][24][25]. Besides cutaneous melanomas, increased expression of cyclin D1 has been reported in uveal melanomas, and now we also confirm in oral melanomas, suggesting that it has an oncogenic role in the pathogenesis of this aggressive neoplasm [13,24,26]. Some studies have also shown that cyclin D1 is associated with unfavorable outcomes in cutaneous melanomas and is an independent risk factor for the development of metastases [25,26].…”

Section: Discussionsupporting

confidence: 92%

Immunohistochemical Expression of p16, p21, p27 and Cyclin D1 in Oral Nevi and Melanoma

Andrade

León

Carlos³

et al. 2012

Head and Neck Pathol

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The acquisition of abnormalities at G1/S is considered a crucial step in the genesis and progression of melanoma. The expression of cell cycle regulators has also been used in various neoplasms as an adjunct to diagnosis. The aim of this study was to compare the expression of p16, p21, p27 and cyclin D1 in oral nevi and melanomas. Expression of these cell cycle regulatory proteins was evaluated by immunohistochemistry in 51 oral melanocytic lesions, including 38 intramucosal nevi and 13 primary oral melanomas. p16 and p27 were highly expressed in intramucosal nevi, whereas p21 and cyclin D1 expression was higher in oral melanomas. The results indicate that p21 and cyclin D1 may be involved in the development of oral melanomas, and eventually they may be useful in the differential diagnoses of oral benign and malignant melanocytic lesions.

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Section: Discussionsupporting

confidence: 92%

Immunohistochemical Expression of p16, p21, p27 and Cyclin D1 in Oral Nevi and Melanoma

Andrade

León

Carlos³

et al. 2012

Head and Neck Pathol

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“…It has been shown that an increase in cell size can regulate proliferation and in particular the progression through the G1 phase of the cell cycle [25]. The tumor suppressor phosphatase and tensin homolog (PTEN) plays a critical role in neural precursor proliferation and growth [26].…”

Section: Gaba a Rs Activation Promotes The Cell Cycle Entry In Neonatmentioning

confidence: 99%

GABAA Receptor Signaling Induces Osmotic Swelling and Cell Cycle Activation of Neonatal Prominin+ Precursors

et al. 2011

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Signal-regulated changes in cell size affect cell division and survival and therefore are central to tissue morphogenesis and homeostasis. In this respect, GABA receptors (GABA A Rs) are of particular interest because allowing anions flow across the cell membrane modulates the osmolyte flux and the cell volume. Therefore, we have here investigated the hypothesis that GABA may regulate neural stem cell proliferation by inducing cell size changes. We found that, besides neuroblasts, also neural precursors in the neonatal murine subependymal zone sense GABA via GABA A Rs. However, unlike in neuroblasts, where it induced depolarization-mediated [Ca 21 ] i increase, GABA A Rs activation in precursors caused hyperpolarization. This resulted in osmotic swelling and increased surface expression of epidermal growth factor receptors (EGFRs). Furthermore, activation of GABA A Rs signaling in vitro in the presence of EGF modified the expression of the cell cycle regulators, phosphatase and tensin homolog and cyclin D1, increasing the pool of cycling precursors without modifying cell cycle length. A similar effect was observed on treatment with diazepam. We also demonstrate that GABA and diazepam responsive precursors represent prominin 1 stem cells. Finally, we show that as in in vitro also in in vivo a short administration of diazepam promotes EGFR expression in prominin 1 stem cells causing activation and cell cycle entry. Thus, our data indicate that endogenous GABA is a part of a regulatory mechanism of size and cell cycle entry of neonatal stem cells. Our results also have potential implications for the therapeutic practices that involve exposure to GABA A Rs modulators during neurodevelopment. STEM CELLS 2011;29:307-319 Disclosure of potential conflicts of interest is found at the end of this article.

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“…10 UM-A < 7, UM-A > 7, NM and UM cell lines (UW-1, OCM-1, SP5.6 and 92.1) were cultured in RPMI medium containing 5% inactivated fetal calf serum (FCS), 2 mM glutamine and standard antibiotics at 37°C in 5% CO 2 .…”

Section: Cell Culturementioning

confidence: 99%

“…The UM-A primary culture, characterized by the presence of hypophosphorylated and unexpectedly inactive antitumoural protein Rb, changed into a phenotypically different cell line after 7 passages. 10 On the basis of extracellular matrix (ECM) invasion assays that showed a low and high degree of metastatic potential in the UM primary cell culture (UM-A < 7) and cell line (UM-A > 7), respectively, we present here the differential proteome analysis of both cultures. The identification of differentially regulated features reveals an increase in the cellular metabolism of the UM-A cell line and, interestingly, a different expression profile of cancer-related proteins.…”

mentioning

confidence: 99%

“…9 We recently applied this approach to obtain the first proteome analysis of a previously well-characterized uveal melanoma primary cell culture named UM-A. 10,11 This analysis represented the first step towards the utilization of proteomics in the study of uveal melanoma tumours and a novel approach to search for potential markers. The UM-A primary culture, characterized by the presence of hypophosphorylated and unexpectedly inactive antitumoural protein Rb, changed into a phenotypically different cell line after 7 passages.…”

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confidence: 99%

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The characterization of the invasion phenotype of uveal melanoma tumour cells shows the presence of MUC18 and HMG‐1 metastasis markers and leads to the identification of DJ‐1 as a potential serum biomarker

Pardo¹,

García²,

Thomas³

et al. 2006

Intl Journal of Cancer

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Uveal malignant melanoma (UM) is the most frequent primary intraocular tumour in adult humans. Because the survival rate of patients with UM has changed little in the past few decades, a better understanding of the molecular events governing UM development and the identification of markers indicating the potential for metastasis at the time of diagnosis are necessary to design improved and more specific treatments. In this study, we investigated UM tumour development by comparing two recently established UM cultures with different invasion potential by twodimensional gel electrophoresis. Protein features expressed differentially were identified by mass spectrometric analysis. Potential markers were assayed in both cultures and in long-term established UM cell lines (UW-1, OCM-1, SP6.5 and 92.1) by Western blotting and their role in invasion analysed using Matrigel membranes. Comparative analysis revealed that UM cultures with lowand high-grade invasion potential differ in their cellular metabolism and, more interestingly, in several cancer-associated proteins, including those implicated in cell adhesion and migration, proliferation and various oncogenes. Our data indicate a correlation between MUC18 and HMG-1 expression and the invasiveness of UM cells. We also demonstrate the expression and secretion of DJ-1 oncoprotein by UM cells. We suggest a possible role for MUC18 and HMG-1 proteins in UM cell invasion. The secretion of DJ-1 by UM cells, and the ability to detect this protein in UM patients' sera implicate it as a potential noninvasive biomarker for this malignancy. ' 2006 Wiley-Liss, Inc.Key words: uveal melanoma; invasion; proteomics; MUC-18; DJ-1 Uveal malignant melanoma (UM) is the most frequent intraocular tumour in adult humans.1 Unlike cutaneous melanoma, uveal melanoma disseminates mainly through the blood stream and preferentially establishes metastases in the liver. Metastatic liver disease is the leading cause of death in uveal melanoma and can develop after a long disease-free interval, which suggests the presence of occult micrometastatic disease at the time the primary eye tumour is diagnosed and treated.2 Unfortunately, advances in eye cancer treatment have not paralleled those made in the management of other types of cancer, and the survival rate of patients with uveal melanoma has changed little in the past few decades.3 A better understanding of the molecular events governing uveal melanoma development and the identification of markers indicating the potential for metastasis at the time of diagnosis are necessary to design improved and more specific treatments. Various clinical and molecular prognostic factors have been suggested in uveal melanoma, but none has proved to be sufficiently useful or viable for routine clinical use. 4,5 Currently, there are many challenging technologies and approaches to identify tumour markers for prognostic and therapeutic purposes.6 Transcriptional studies alone are not sufficient, with several investigators reporting a poor correlation between mRNA and p...

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Abnormal cell cycle regulation in primary human uveal melanoma cultures

Cited by 25 publications

References 45 publications

Immunohistochemical Expression of p16, p21, p27 and Cyclin D1 in Oral Nevi and Melanoma

Immunohistochemical Expression of p16, p21, p27 and Cyclin D1 in Oral Nevi and Melanoma

GABAA Receptor Signaling Induces Osmotic Swelling and Cell Cycle Activation of Neonatal Prominin+ Precursors

The characterization of the invasion phenotype of uveal melanoma tumour cells shows the presence of MUC18 and HMG‐1 metastasis markers and leads to the identification of DJ‐1 as a potential serum biomarker

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