BRAFV600E mutations in malignant melanoma are associated with increased expressions of BAALC

<p>Abstract</p> <p>Bachground</p> <p>Activating <it>BRAF </it>mutations are present in approximately 50% of melanomas. Although different downstream target genes of the most common mutant V600E have been identified, the contribution of activating <it>BRAF </it>mutations to malignant transformation needs further clarification.</p> <p>Methods</p> <p>Microarray gene analysis was performed for human melanoma cell lines harboring BRAF^V600Emutations in comparison to cell lines without this mutation.</p> <p>Results</p> <p>This analysis revealed a more than two fold down-regulation of 43 and an increase of 39 gene products. <it>BAALC </it>(<it>Brain and acute Leukaemia, cytoplasmatic</it>) was most prominently regulated, since it was up-regulated in mutated cell lines by a mean of 11.45. Real time PCR analyses with RNA from melanoma cell lines (n = 30) confirmed the <it>BRAF</it>-activation dependent up-regulation of <it>BAALC</it>.</p> <p>Conclusion</p> <p><it>BAALC</it>, which has been associated with cell dedifferentiation and migration, may function as a downstream effector of activating <it>BRAF </it>mutations during melanomagenesis.</p

High-Level Expression of Wild-Type p53 in Melanoma Cells is Frequently Associated with Inactivity in p53 Reporter Gene Assays

Background: Inactivation of the p53 pathway that controls cell cycle progression, apoptosis and senescence, has been proposed to occur in virtually all human tumors and p53 is the protein most frequently mutated in human cancer. However, the mutational status of p53 in melanoma is still controversial; to clarify this notion we analysed the largest series of melanoma samples reported to date. Methodology/Principal Findings: Immunohistochemical analysis of more than 180 melanoma specimens demonstrated that high levels of p53 are expressed in the vast majority of cases. Subsequent sequencing of the p53 exons 5–8, however, revealed only in one case the presence of a mutation. Nevertheless, by means of two different p53 reporter constructs we demonstrate transcriptional inactivity of wild type p53 in 6 out of 10 melanoma cell lines; the 4 other p53 wild type melanoma cell lines exhibit p53 reporter gene activity, which can be blocked by shRNA knock down of p53. Conclusions/Significance: In melanomas expressing high levels of wild type p53 this tumor suppressor is frequently inactivated at transcriptional level

Kaposiform hemangioendothelioma with distant lymphangiomatosis without an association to Kasabach-Merritt-Syndrome in a female adult!

Claudia S Vetter-Kauczok1, Philipp Str&ouml;bel2, Eva B Br&ouml;cker1, J&uuml;rgen C Becker11Department of Dermatology, Julius-Maximilians-University Wuerzburg, Wuerzburg, Germany; 2Department of Pathology, Ruprecht-Karls-University Mannheim, Mannheim, GermanyAbstract: Kaposiform hemangioendothelioma (KHE) is a locally aggressive vascular tumor which usually occurs in infants. Clinically it appears as ill-defined red to purple indurated plaque. KHE is commonly associated with Kasabach-Merritt syndrome (KMS) and lymphangiomatosis. Microscopically, the tumor is composed of infiltrating lobulated nodules with slitlike or crescentic vessels which are poorly canalized and lined by spindle shaped endothelial cells. We report a 36-year old female who developed a reddish tumor on the chest. Histological examination revealed a KHE, which was clinically not associated with thrombocytopenia or bleeding complications, but lymphangiomatosis at the right submandibular region. The association of KHE in a female adult with lymphangioma rather than KMS in this case supports the hypothesis that such an association may represent a benign subform of this disease in an adult and excision seems to be curative.Keywords: Kasabach-Merritt-Syndrome, Kaposiform hemangioendothelioma, lymphangiomatosi

Sex-specific therapeutic strategies based on neuroactive steroids: In search for innovative tools for neuroprotection

Different pathologies of the central and peripheral nervous system show sex differences in their incidence, symptomatology and/or neurodegenerative outcome. These include Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple sclerosis, traumatic brain injury, stroke, autism, schizophrenia, depression, anxiety disorders, eating disorders and peripheral neuropathy. These sex differences reveal the need for sex-specific neuroprotective strategies. This review article and other manuscripts published in this issue of Hormones and Behavior analyze possible sex-specific therapeutic strategies based on neuroactive steroids. In particular in our introductory article, the possibility that sex differences in the levels or in the action of neuroactive steroids may represent causative factors for sex differences in the incidence or manifestation of pathologies of the nervous system is considered. © 2009 Elsevier Inc. All rights reserved.Peer Reviewe