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)

The human breast epithelial cell line, MCF-10A, derived from tissue from a woman undergoing a cutaneous mastectomy for fibrocystic breast disease, is negative for estrogen receptor expression, has undergone minimal genetic changes, retains many of the characteristics of normal breast epithelium and fails to exhibit growth in nude mice. When transfected with a functional copy of the estrogen receptor, both ER and MDM2 expression are negatively regulated by the presence of increasing concentrations of estradiol, as previously reported. We obtained the MCF-10A cell line from the American Type Culture Collection and confirmed that it was negative for ER expression. After approximately 20 passages under differing growth conditions, one subline was determined to be positive for ER expression. Growth of this ER-positive subline in phenol red-free media supplemented with charcoal-dextran stripped serum in the presence of nanomolar concentrations of estradiol failed to modulate ER and MDM2 expression, and induced expression of both pS2 and cathepsin D. Simultaneously with these observations, we observed that this subline, unlike the parent MCF-10A line, overexpressed P53 protein with a nuclear localization. Intermediate levels of the P53-inducible protein p21 WAF1/Cip1 were also detected in the ER-positive subline whereas levels of this protein in the parent subline were barely detectable, as measured by immunohistochemical methods. We conclude from these studies that ER expression and P53 alteration may constitute early steps in progression of malignant potential for breast cancer development.
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PMID:Spontaneous conversion to estrogen receptor expression by the human breast epithelial cell line, MCF-10A. 1020 82

Endometrial adenocarcinoma is the most common malignant neoplasm of the female genital tract and, despite its relative frequency, the molecular events that contribute to the development and progression of the lesion remain poorly understood. The normal human endometrium is characterized by hormone-dependent variations during the menstrual cycle. This tightly controlled system is disturbed in endometrial hyperplasia and carcinomas and a series of changes initiate and promote progression towards the malignant phenotype. These changes can be subdivided into discrete steps, involving activation of oncogenes, inactivation of tumour suppressor genes, deregulation of cell cycle regulators or other proteins involved in tumour invasion and progression. Immunohistochemical expression of different biomarkers such as hormone receptor status (ER, PR), proliferation associated indices (PCNA, MIB1), oncogene (c-erbB-2), tumour suppressor gene products (pRb, p53 protein), cell cycle related proteins (cyclin D1, cyclin E, p21/WAF1), anti-apoptotic protein (bcl-2), adhesion molecule (CD44s), proteolytic enzyme (cathepsin D), heat shock protein (hsp27) and metallothionein (MT) has shown the contribution of these molecules to endometrial carcinogenesis in a hormone-dependent or independent manner as an early or late event. In addition, these biomarkers seem to be correlated with tumour differentiation or myometrial invasion, and therefore could be considered as indicators of the biological behaviour of endometrial carcinoma. Furthermore, the interrelationships of these molecular markers show that these genetic dysregulations could be implicated in the control of cell proliferation and differentiation, and thereby in the multistep process of endometrial carcinogenesis.
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PMID:Immunohistochemical tumour markers in endometrial carcinoma. 1612 80

Recent studies disclosed that autophagy is induced during and facilitates the process of senescence. Given that biliary epithelial cells (BECs) in damaged small bile ducts in primary biliary cirrhosis (PBC) show senescent features, we examined an involvement of autophagy in the process of biliary epithelial senescence in PBC. We examined immunohistochemically the expression of microtubule-associated proteins-light chain 3beta (LC3), a marker of autophagy, in livers taken from the patients with PBC (n=37) and control livers (n=75). We also examined the co-localization of LC3 with autophagy-related cathepsin D, lysosome-associated membrane protein-1 (LAMP-1), and senescent markers, p16(INK4a) and p21(WAF1/Cip1). We examined the effect of autophagy inhibitor (3-methyladenine) on the induction of cellular senescence and senescence-associated secretion (CCL2 and CX3CL1) in cultured murine BECs. The expression of LC3 was specifically seen in vesicles in BECs in the inflamed and damaged small bile ducts in PBC, when compared with non-inflamed small bile ducts in PBC and in control livers (P<0.01). The expression of LC3 was closely related to the expression of cathepsin D, LAMP-1, and senescent markers. In cultured BECs, oxidative stress, DNA damage, and serum deprivation induced cellular senescence, when compared with control and the inhibition of autophagy significantly decreased the stress-induced cellular senescence (P<0.01). Furthermore, the secretion level of CCL2 and CX3CL1 increased significantly by various stress and suppressed by the inhibition of autophagy (P<0.01). In conclusion, autophagy is specifically seen in the damaged small bile ducts along with cellular senescence in PBC. The inhibition of autophagy suppressed cellular senescence in cultured cells. These findings suggest that autophagy may mediate the process of biliary epithelial senescence and involve in the pathogenesis of bile duct lesions in PBC.
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PMID:Autophagy mediates the process of cellular senescence characterizing bile duct damages in primary biliary cirrhosis. 2021 59