Genetic alterations frequently are involved in the development of a pituitary adenoma in young age. We here characterize the functional role of a deletion in CDKN1B 5'-UTR region (c.-29_-26delAGAG) identified in an acromegalic patient that developed a growth hormone in pituitary adenoma during childhood. Our results show that the identified novel heterozygous deletion in the CDKN1B 5'-UTR region associates with a reduction in CDKN1B mRNA levels, a predicted altered secondary mRNA structure, and a reduced CDKN1B 5'-UTR transcriptional activity in vitro. The patient displayed loss of heterozygosity in the same CDKN1B 5'-UTR region at tissue level and the 5'UTR region containing the deleted sequence encompasses a GRE. These findings indicate that the identification of functional alterations of newly discovered genetic derangements need to be fully characterized and always correlated with the clinical manifestations.

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We found that Magmas protein (Tim16) in the MCF7 cell line is highly expressed as compared to MDA-MB231 cells and MCF12A. Our data show that treatment with compound 5 did not influences cell viability in the 3 cell lines , while Doxorubicin decrease this parameter by 20-30%. Only in MCF7 co-treatment with compound 5 enhance the antiproliferative effects of Doxorubicin. MitoTox Glo assay shows that in MCF7 cells the enhancing effects of compound 5 on Doxorubicin effects are due to mitochondrial toxicity. Finally we found that co-treatment with compound 5 and Doxorubicin in MCF7 significantly decreases BrDu incorporation, suggesting antiproliferative effects of the combination of these drugs.