Using these assays we show that determination of pS2 gene expression allows the definition of subclasses of estrogen-receptor-containing breast cancers that may be used to more precisely identify estrogen-dependent tumors.
To investigate the expression and possible role of pS2 protein as a predictor of tumor recurrence in superficial transitional cell carcinoma of the bladder and to determine its relation with tumor stage, grade, size, number, recurrence and proliferative activity.
At completion of the study, half of the animals per treatment group were killed and tumors collected for evaluation of cellular proliferation and estrogen-responsive pS2 gene expression.
The expression of the pS2 gene, pS2 protein assays in tumor cytosols and more recently pS2 detection by immunocytochemistry, have been described in several series of breast cancers.
The 5' flanking region of the pS2 gene contains a complex enhancer region responsive to oestrogens, epidermal growth factor, a tumour promoter (TPA), the c-Ha-ras oncoprotein and the c-jun protein.
In situ hybridization to some of the p27-overexpressing tumors showed that the p27 RNA is localized in cancer cells and sometimes also in fibroblastic cells of tumor stroma. p27 RNA levels in the tumors did not correlate with the presence of estrogen receptor or with the expression of the estrogen-induced pS2 gene.
This suggests that the pS2 gene expression detected in nonmalignant tissue may be related to early premalignant changes of prostate glands harboring significant carcinomas.
Otherwise, no overlapping of pS2 protein values was obtained between ER-positive and ER-negative carcinomas within defined unfavorable menopausal - and histologic grade-related expression of pS2 protein subgroups.
RNA blot hybridization analysis revealed that pS2 gene was expressed well in two (MKN-45 and KATO-III; derived from poorly differentiated adenocarcinoma) but not in three cell lines (MKN-1, MKN-28 and MKN-74; from well differentiated adenocarcinoma), suggesting that expression of the pS2 gene depends on the state of cell differentiation.
This suggests that the pS2 gene expression detected in nonmalignant tissue may be related to early premalignant changes of prostate glands harboring significant carcinomas.
These data clearly indicate that the breast-cancer-associated pS2 protein also plays an as yet undetermined role in the tumorigenesis of human colorectal carcinomas.
Recent studies have revealed that forebrain specific conditional knockouts of PS1 and PS2 genes (cPSKO) cause both neuronal degeneration and memory loss without evidence of formation of amyloid plaques.
Although the mechanism(s) whereby the PS-1 and PS-2 gene mutations operate remains unclear, it seems from the present study that the effect of the PS-2 gene mutation on the brain is much less severe, at least as far as Abeta deposition is concerned, than that of the PS-1 mutation, which seems to confer a much earlier and a much more aggressive development of AD.
Mutations in APP and PS-1 and PS-2 genes that are associated with early-onset, autosomal, dominantly inherited AD, in addition to the at-risk gene polymorphisms responsible for late-onset AD, all indicate a direct and early role of Aβ in the pathogenesis of AD.
While genetic mutations in amyloid precursor protein and presenilin-1 and -2 (PS1 and PS2) genes cause early-onset familial AD, the etiology of sporadic AD is not fully understood.
Autosomal dominant familial AD (FAD), linked to mutations in presenilin (PS1 and PS2) genes or the amyloid precursor protein (APP) gene, shows brain abnormalities (e.g., neurofibrillary tangles, deposits of .-amyloid A., and death of subsets of neurons) similar to those that occur in sporadic AD, the risk of which is enhanced by the presence of one or two copies of apolipoprotein E4 (apoE4) alleles.
An increased production of Abeta-42 by mutation of PS2 genes promotes caspase expression and is associated with the Cox-2 found in the brain of AD patients.