Polymorphism C in the serotonin transporter gene in depression-free elderly patients with vascular dementia.

BACKGROUND: Genotypes of the solute carrier family 6 (neurotransmitter transporter, serotonin) member 4 (SLC6A4) have been variously associated with depression, obsessive-compulsive disorder, memory impairment, and anxiety. Less clear are data regarding their association with severe dementia, in particular with vascular dementia (VaD). AIMS: To evaluate the possible involvement of different SLC6A4 genotypes/haplotypes in VaD. METHODS: The analysis of the 3 markers rs3813034, rs140701 and rs4795541 spanning the SLC6A4 locus was made in 541 consecutive patients clinically diagnosed as having VaD (n = 372) or no cognitive impairment (n = 169) attending a geriatric ward. A community-dwelling sample of 353 healthy subjects, as a reference for the genetic frequencies in the recruitment area, was also included in the study. All patients and subjects were free from any symptoms of depression, obsessive-compulsive disorder and anxiety. A complete neuroimaging documentation was available for all patients. RESULTS: No important differences were observed in genotype distribution across the study groups. Similarly, no important differences were observed in haplotype distribution when a 3-point analysis was made. CONCLUSION: Our findings suggest that polymorphism C in the promoter region of the SLC6A4 gene plays a minor role, if any, in the pathogenesis of VaD.

Genomic instability and increased expression of BUB1B and MAD2L1 genes in ductal breast carcinoma.

In a series of invasive ductal breast carcinoma, we investigated the status of chromosomal and intrachromosomal instability by fluorescence in situ hybridisation and determined the level of mRNA expression for two genes involved in the mitotic spindle checkpoint pathway, BUB1B and MAD2L1. All breast cancers demonstrated higher chromosomal instability rates in tumor samples (average: 56.86%, range: 36.24-76.78%) than in controls (average: 11.54%, range: 9.91-14.84%) (P<0.0001). As well as intrachromosomal instability rates were elevated in tumor (average: 18.45% range: 8.34-35.8%) as compared with controls (average: 4.18% range: 3.47-4.81%) (P<0.0001). An increase in BUB1B and MAD2L1 transcripts was demonstrated in the majority of the tumor tested. BUB1B mRNA levels but not MAD2L1 levels correlated with intrachromosomal instability (r=0.722, P=0.018).

Osteopontin enhances the cell proliferation induced by the epidermal growth factor in human prostate cancer cells.

BACKGROUND: Susceptibility to extracellular matrix and growth factors has been demonstrated to play a critical role in the development of prostate cancer (PCa) metastases. The aim of this study was to elucidate some mechanisms by which stroma controls tumor progression. METHODS: In our study we tested the growth ability of the LNCaP human prostatic cell line in steroid-free culture conditions in response to osteopontin (OPN), a non-collageneous matrix protein, localized in large amounts in the bone. RESULTS: In the LNCaP cell model, OPN stimulates cell proliferation in serum-free medium and colony growth at high dilution but this effect is visible only in presence of epidermal growth factor (EGF). Proliferation induced by OPN is accompanied by a sustained activation of EGF receptor (EGFR) whose phosphorylation is detectable up to 12 hr after treatment in association with EGF. The colocalization of integrin beta1, a ligand of OPN, and of EGFR on the cellular membrane, suggests that the association of these cell surface receptors may be the principal mechanism involved in the long-term activation of the EGFR. CONCLUSIONS: Our data describe a new possible mechanism involved in the establishment of bone metastases which may also account for the formation of androgen-independent cellular clones, frequently responsible of the clinical progression of PCa.