Dysregulated expression of Fau and MELK is associated with poor prognosis in breast cancer

Introduction  

Programmed cell death through apoptosis plays an essential role in the hormone-regulated physiological turnover of mammary tissue. Failure of this active gene-dependent process is central both to the development of breast cancer and to the appearance of the therapy-resistant cancer cells that produce clinical relapse. Functional expression cloning in two independent laboratories has identified Finkel–Biskis–Reilly murine sarcoma virus-associated ubiquitously expressed gene (Fau) as a novel apoptosis regulator and candidate tumour suppressor. Fau modifies apoptosis-controller Bcl-G, which is also a key target for candidate oncoprotein maternal embryonic leucine zipper kinase (MELK).     

Lack of expression of inhibitory KIR3DL1 receptor in patients with natural killer cell-type lymphoproliferative disease of granular lymphocytes

Background

Natural killer cell-type lymphoproliferative disease of granular lymphocytes is a disorder characterized by chronic proliferation of CD3⁻CD16⁺ granular lymphocytes. By flow cytometry analysis, we previously demonstrated a dysregulation in killer immunoglobulin-like receptor (KIR) expression in natural killer cells from patients with this lymphoproliferative disease, the activating KIR receptors being mostly expressed. We also found that patients with natural killer cell-type lymphoproliferative disease of granular lymphocytes usually had KIR genotypes characterized by multiple activating KIR genes.

Design and Methods

We investigated the mRNA levels of the KIR3DL1 inhibitory and the related KIR3DS1 activating receptors in 15 patients with natural killer cell-type lymphoproliferative disease of granular lymphocytes and in ten controls. These genes are usually expressed when present in the genome of the Caucasian population.

Results

We demonstrated the complete lack of KIR3DL1 expression in most of the patients analyzed, with the receptor being expressed in 13% of patients compared to in 90% of controls (P<0.01). Interestingly, studies of the methylation patterns of KIR3DL1 promoter showed a significantly higher methylation status (0.76 ± 0.12 SD) in patients than in healthy subjects (0.49±0.10 SD, P<0.01). The levels of expression of DNA methyl transferases, which are the enzymes responsible for DNA methylation, did not differ between patients and controls.

Conclusions

In this study we showed, for the first time, a consistent down-regulation of the inhibitory KIR3DL1 signal due to marked methylation of its promoter, thus suggesting that together with the increased expression of activating receptors, the lack of the inhibitory signal could also play a role in the pathogenesis of natural killer cell-type lymphoproliferative disease of granular lymphocytes.     

Developmental patterns of Ki-67, bcl-2 and caspase-3 proteins expression in the human upper jaw

The distribution of the Ki-67, bcl-2 and caspase-3 proteins was immunohistochemically analyzed in the developing human upper jaw (5th-10th gestational weeks).During this period, proliferative activity gradually decreased from higher levels at the earliest stages (50-52%) to lower levels, both in the jaw ectomesenchyme and in the epithelium. The highest expression of bcl-2 protein was found in the epithelium and ectomesenchyme of areas displaying lower rates of cell proliferation. High levels of caspase-3 protein were detected during the earliest stages of jaw development, indicating an important role for apoptosis in morphogenesis of early derivatives of the maxillary prominences. The number of Ki-67, bcl-2 and caspase-3 positive cells changed in a temporally and spatially restricted manner, coincidently with upper jaw differentiation. While apoptosis might control cell number, bcl-2 could act in suppression of apoptosis and enhancement of cell differentiation. A fine balance between cell proliferation (Ki-67), death (caspase-3) and cell survival (bcl-2) characterized early human upper jaw development. A rise in the number of apoptotic cells always temporally coincided with the decrease in number of surviving bcl-2 positive cells within the palatal region. Therefore, the upper jaw development seems to be controlled by the precisely defined expression of genes for proliferation, apoptosis and cell survival.     

Galactocele: an unusual cause of breast enlargement in children

Galactoceles in children, either cystic or pseudotumors, are described in the literature as a rare cause of increasing breast size and can appear in males. We report a case of galactocele in a 15-month-old male, treated at our institution. The patient presented with a tumor in the right breast that had appeared 6 months earlier with no pain, signs of inflammation, or nipple secretion. Twelve cases found in the literature emphasize the importance of including galactocele in the differential diagnosis of benign breast masses in infancy.