Expression of Hormone Receptors, Cathepsin D, and HER-2/neu Oncoprotein in Normal Colon and Colonic Disease

Galandiuk, Susan; Miseljic, Slobodan; Yang, Ai-Ru; Early, Michelle; McCoy, Matthew; Wittliff, James L.

doi:10.1001/archsurg.1993.01420180035007

Cited by 30 publications

(21 citation statements)

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“…3,11 It also has mitogenicproperties 12 and facilitates the releaseof angiogenic factor and basic fibroblast growth factor, stimulating neovascularization. 13 Galanduiket al, 14 using immunoassay, showed increased CD levels in neoplastic colon tissues with respect to the normal colon, regardless of whether cells expressed this protease. Theodoropouloset al, 1 performing immunohistochemistry with a monoclonal antibody, detected CD in tumor and stromal cells in colon cancer specimens.…”

Section: Discussionmentioning

confidence: 97%

Expression of Cathepsin D in Colorectal Adenocarcinomas: Correlation with Clinicopathologic Features

et al. 2003

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F Yilmaz, AK Uzunlar, N Kilinc, HG Yilmaz, Expression of Cathepsin D in Colorectal Adenocarcinomas: Correlation with Clinicopathologic Features. 2003; 23(3-4): 208-211 Colorectal carcinoma is the second most frequent carcinoma, after carcinoma of the lung, in Western countries. 1 The prognosis for patients with colorectal carcinoma seems to be related mainly to the control of both progression and metastasis of the malignant tumor. In metastasis, proteolytic enzymes play an important role in mediating passage of the malignant cell through the cell membrane.2 Proteases are thought to be important factors for tumor invasion and metastasis because they can degrade extracellular matrices and basement membranes, 3,4 which play a defensive role for tumor invasion and metastasis.5 Cathepsin D (CD) is known to be a lysosomal acid protease that is mainly included in intracellular protein catabolism and is inducible by estrogens.6 Therefore, many investigators have studied intensively the role of CD in breast carcinomas. These studies have suggested that the expression of CD is correlated with the invasion and metastasis of breast carcinomas, 7-9 but the role of CD expression in predicting prognosis or invasive potential in colorectal carcinoma is unknown. 1In this study, we evaluated the expression of CD in a series of colorectal carcinomas and its correlation with conventional clinicopathologic features such as age, gender, tumor size, tumor grade and Dukes' stage. Patients and MethodsTissue samples were obtained from the surgical specimens of 100 primary colorectal adenocarcinomas. All specimens were collected at the Department of Pathology, Dicle University Hospital, Diyarbakir, Turkey between 1995 and 2000. The clinical data were obtained from pathological reports. The specimens were fixed in formalin and embedded in paraffin. Consecutive 4-mm-thick sections were stained with hematoxylin and eosin for histological diagnosis.Histologically, all colorectal carcinomas were adenocarcinomas. The grade of differentiation was high in 17, moderate in 58, and low in 25 cases. Staging of cases was pathological only (Dukes' stage A, B and C). There were 10 cases of stage A, 31 cases of stage B and 59 cases of stage C. The mean age of the patients was 53.7 years (range,24 to 80 years), and the male/female ratio was 1.3 (56/44). Most adenocarcinomas were located in the rectosigmoid (n=65).One or two blocks from each tumor were stained for immunohistochemical analysis using the Avidin-Biotin and immunoperoxidase methods. Additional 4-mm-thick sections were cut from paraffin blocks. After blockage of endogenous peroxidase with H 2 O 2 in methanol for 30 minutes, sections were immersed in citrate buffer (pH=6.0) in a microwave-resistant container. Subsequently, the sections were incubated with a protein-blocking solution for five minutes and then incubated with a mouse anti-human cathepsin D monoclonal antibody (Dako, Carpinteria, USA). Immunoperoxidase detection was employed, using the diaminobenzidine substrate (DAB). Counter s...

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Section: Discussionmentioning

confidence: 97%

Expression of Cathepsin D in Colorectal Adenocarcinomas: Correlation with Clinicopathologic Features

et al. 2003

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“…The results of recent publications on colonic mucosal EGFR activity in IBD bring discrepant conclusions. Galandiuk and Trzcinski observed high expression of EGFR in colonic mucosa in a murine model of colitis, which according to the authors suggested a role of this receptor in promoting the inflammatory response [6][7][8][9].…”

Section: Discussionmentioning

confidence: 99%

“…High expression of ErbB mucosal receptors (EGFR family member) was shown in active phases of inflammatory diseases -IBD [6][7][8][9], asthma [10], rheumatoid arthritis [11]. On the other hand, other authors suggest that EGFR inhibition might cause NFκB activation, resulting in an inflammatory response [12,13].…”

Section: Introductionmentioning

confidence: 99%

Expression of epithelial growth factor receptor, tumor necrosis factor-α and nuclear factor κB in inflammatory bowel diseases

Durko¹,

Stasikowska-Kanicka²,

Wągrowska-Danilewicz³

et al. 2013

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Expression of epithelial growth factor receptor, tumor necrosis factor-α α and nuclear factor κ κB in inflammatory bowel diseases Ekspresja receptora dla naskórkowego czynnika wzrostu, czynnika martwicy nowotworów α i czynnika jądrowego κB w nieswoistych chorobach zapalnych jelit K Ke ey y w wo or rd ds s: : inflammatory bowel diseases, epithelial growth factor receptor, tumor necrosis factor-α, nuclear factor κB. S Sł ło ow wa a k kl lu uc cz zo ow we e: : choroby zapalne jelit, receptor dla naskórkowego czynnika wzrostu, czynnik martwicy nowotworów α, czynnik jądrowy κB. Original paper/Artykuł oryginalny Abstract I In nt tr ro od du uc ct ti io on n: : The role of epithelial growth factor receptor (EGFR) in inflammatory bowel diseases (IBD) pathogenesis has not been fully elucidated. Overexpression of EGFR in colonic inflamed mucosa in patients with IBD has been observed by some authors. Moreover some studies confirm the role of EGFR in upregulating nuclear factor κB (NF-κB) and tumor necrosis factor-α (TNF-α) expression, which may lead to pronounced inflammatory response in IBD. A Ai im m: : To evaluate the expression of EGFR, NF-κB and TNF-α in remission and active phase of Crohn disease (CD) and ulcerative colitis (UC). M Ma at te er ri ia al l a an nd d m me et th ho od ds s: : Biopsy specimens from colonic mucosa were taken at colonoscopy from 62 patients with CD, 92 patients with UC and from 18 healthy subjects with normal colonic mucosa (control). The expression of EGFR, NF-κB and TNF-α was evaluated by immunohistochemical staining. R Re es su ul lt ts s: : The colonic mucosal immunoexpression of EGFR in active phase of IBD was significantly lower compared to the remission. The immunoexpression of NF-κB and TNF-α was si gnificantly higher in the active disease phase of IBD than in remission. The results suggest that EGFR does not promote inflammation in IBD but most probably is involved in mucosal regeneration in IBD. C Co on nc cl lu us si io on ns s: : High expression of NF-κB and TNF-α in active phases of UC and CD confirm their proinflammatory role in these diseases.

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“…Cathepsin D has also been found at a high lcvcl in colon cancer (Galandiuk et al, 1993). We have previously reportcd that the HT-29 colon carcinoma cell line secretes pro-cathepsin D in its culture medium (Huet et al, 1994), suggesting that this proteinase might be also involved in the neoplastic progression of colon cancers.…”

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confidence: 93%

Regulation of cathepsin D dependent on the phenotype of colon carcinoma cells

et al. 1996

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Int. J. Cancer: 68,479-484 (1996) 0 1996 Wilcy-Liss, Inc. In human skin fibroblasts, cathepsin D is synthesised as a glycosylated precursor form of M, 53,000 with 2 asparaginelinked oligosaccharide side chains in the rough endoplasmic reticulum (Hasilik and Von Figura, 1981; Gieselman et al., 1983). A portion of these N-linked oligosaccharides may become phosphorylated or converted into complex oligosaccharides in the Golgi apparatus (Hasilik and Von Figura, 1981; Giesclman et al., 1983). Phosphomannosyl residucs are lysosoma1 targcting signals which will bind to the mcmbrancassociated mannose-6-phosphate specific receptors (MPRs) in the trans-Golgi network (Dahms et al., 1989). During transport to lysosomes, the precursor form is successively converted into an intermediate M, 47,000 form by cleavage of the pro-peptide in a pre-lysosomal compartment and then into the mature M, 31,000 form found in lysosomes (Gieselman et al., 1983). REGULATION OF CATHEPSIN D DEPENDENT ON THE PHENOTYPE OF COLON CARCINOMA CELLSSylvianeThe oestrogen-stimulated over-cxprcssion of cathepsin D in breast cancer cells has becn suggested to induce a saturation of the mannose-6-phosphatc/IGF-II receptor that Icd to the abnormal secretion of the pro-enzyme (Rochefort et al., 1990). Subsequently, intracellular targeting of cathepsin D was also shown to occur in a mannose-6-phosphate indcpendent manner in HepG2 cells (Rijnboutt et al., 1991a, b ) and breast cancer cells (Capony et al., 1994). In the MPR indcpendent transport in HepG2 cells, cathepsin D also becomes transiently membrane-associated in the Golgi apparatus through binding to an M, 72,000 pro-saposin form (Zhu and Conner, 1994). After delivery to lysosomes and subsequent proteolytic processing, the complex is dissociated and both proteins are released from the membrane. In addition, pro-cathepsin D associates to an M, 68,000 pro-saposin to form a soluble complex.By Western blotting, we have previously shown that the HT-29 colon carcinoma cell line, which contains >95% undiffcrentiatcd HT-29 cclls, secretes pro-cathepsin D in the culture medium, whcreas a subpopulation derived from this cell line, which contains differentiated mucin-secreting HT-29 cells, appears unable to secrete the pro-enzyme. Furthermore, using immunocytochcmistry, we have found that cathepsin D is localised, like mucins, in the apical compartment of the cells, under the brush border (Huct et al., 1994).These observations Icd us to examine the synthesis and intracellular trafficking of cathepsin D in the HT-29 cell line, composed of > 95% undifferentiated cells, and in different types of differentiated colon carcinoma cells: differentiated mucin-secreting HT-29 goblet cells, obtained by a stepwise adaptation to the anti-cancer drug methotrcxatc ( M) (Ixsumeur et al., 1990); differentiated cnterocyte-like HT-29 cells, selected by hexose deprivation (Lcsumeur et al., 1991); and Caco-2 cells, which spontaneously display structural and functional differentiation characteristics of mature enterocytcs at late c...

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Expression of Hormone Receptors, Cathepsin D, and HER-2/neu Oncoprotein in Normal Colon and Colonic Disease

Abstract: Further analyses are needed to determine which parameters are related to and possibly predictive of increased carcinoma risk.

Cited by 30 publications

References 18 publications

Expression of Cathepsin D in Colorectal Adenocarcinomas: Correlation with Clinicopathologic Features

Expression of Cathepsin D in Colorectal Adenocarcinomas: Correlation with Clinicopathologic Features

Expression of epithelial growth factor receptor, tumor necrosis factor-α and nuclear factor κB in inflammatory bowel diseases

Regulation of cathepsin D dependent on the phenotype of colon carcinoma cells

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