Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-seven plurihormonal and 21 growth hormone- prolactin- (GH- PRL-) mixed cell adenomas obtained from patients with acromegaly undergoing transnasal-transsphenoidal surgery were investigated immunohistochemically for expression of Epidermal Growth Factor (EGF), Transforming Growth Factor alpha (TGF alpha), Insulin-like Growth Factor-1 (IGF-1), Estrogen Receptor-Related Protein (ERRP), Multidrug Resistance Marker (MDRM), Protein Kinase C (PKC), Gs alpha,. Cathepsin D and p53. Five plurihormonal adenomas grew invasively. The panel of markers used in this study represents a selection of functional and proliferative markers thought to be associated with the function and development of pituitary adenomas. Our results imply that the growth factors (EGF, TGF alpha, IGF-1), the cell signalling protein Gs alpha and the MDRM are expressed by both types of pituitary adenomas in a similar pattern. Non-invasive GH-PRL-mixed cell adenomas showed an increased expression of IGF-1, TGF alpha and MDRM compared to non-invasive plurihormonal adenomas. No factor was found which would reliably distinguish between invasive and non-invasive adenomas. We failed to confirm the findings of others that p53 and cathepsin D might be indicators of tumor aggressiveness. A participation of ERRP and PKC in the development of bi- and plurihormonal adenomas with acromegaly appears unlikely, as the immunostains were all negative.
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PMID:Markers of function and proliferation in non-invasive and invasive bi- and plurihormonal adenomas of patients with acromegaly: an immunohistochemical study. 1050 79

Perturbations of the insulin-like growth factor (IGF) axis, including the autocrine production of IGFs, IGF binding proteins (IGFBPs) and IGFBP proteases such as prostate specific antigen (PSA), and cathepsin D have been identified in prostate, lung and breast cancer cells and tissues. Serum IGFBP-3 levels have been found to be negatively correlated to the risk of cancer. Interestingly, IGFBP-3 is a potent inhibitor of IGF action and also mediates apoptosis via an IGF-independent mechanism. Recent case-control studies have found an approximately 10% increase in the serum levels of IGF-I in patients with prostate, breast and lung cancers, which are among the most frequently diagnosed cancers. While the studies indicate an association between serum IGF-I levels and cancer risk, causality has not been established. Thus, serum IGF-I level may actually be a confounding variable, serving as a marker for autocrine tissue IGF-I production. Growth hormone (GH) therapy raises both IGF-I and IGFBP-3 levels in serum. However, the role of GH in controlling prostate, breast and lung growth and carcinogenesis remains unclear from animal studies. Increased GH levels as seen in acromegaly have been associated with benign prostatic hyperplasia but not with prostate, breast or lung cancers, although colon cancer mortality may be increased. Should serum IGF-I levels be proven to play a causal role in the pathogenesis of cancer, interpreting the risk associated with therapies such as GH replacement must take into account both the duration of exposure and the risk magnitude associated with the degree of serum IGF-I elevation. Since GH-deficient patients often have a subnormal IGF-I serum level, which normalizes on therapy, their cancer risk on GH therapy probably does not increase substantially above that of the normal population. Until further research in the area dictates otherwise, ongoing surveillance and routine monitoring of IGF-I levels in GH recipients should become standard of care.
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PMID:IGFs and human cancer: implications regarding the risk of growth hormone therapy. 1059 43