EGF induces the expression of matrilysin in the human prostate adenocarcinoma cell line, LNCaP

Sundareshan, Padma; Nagle, Raymond B.; Bowden, G. Timothy

doi:10.1002/(sici)1097-0045(19990801)40:3<159::aid-pros3>3.0.co;2-w

Cited by 21 publications

(10 citation statements)

References 36 publications

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“…The subsequent loss of androgen dependence in late-stage PCa might be expected to cause a decrease in ADAM-10 because IGF-I alone was unable to increase ADAM-10 in vitro. However, because ADAM-10 is maintained at equivalent or greater levels in cancer glands in vivo (as demonstrated by immunohistochemistry), it would appear that additional regulatory factors, such as EGF [which has also been found to specifically up-regulate the metalloprotease matrilysin (MMP-7) in LNCaP cells (11)], are involved in regulating ADAM-10 expression.…”

Section: Adam-10 In Prostate Cancersupporting

confidence: 75%

Expression of the Disintegrin Metalloprotease, ADAM-10, in Prostate Cancer and Its Regulation by Dihydrotestosterone, Insulin-Like Growth Factor I, and Epidermal Growth Factor in the Prostate Cancer Cell Model LNCaP

McCulloch

Akl

Samaratunga

et al. 2004

Clinical Cancer Research

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Purpose:The disintegrin metalloprotease ADAM-10 is a multidomain metalloprotease that is potentially significant in tumor progression due to its extracellular matrix-degrading properties. Previously, ADAM-10 mRNA was detected in prostate cancer (PCa) cell lines; however, the presence of ADAM-10 protein and its cellular localization, regulation, and role have yet to be described. We hypothesized that ADAM-10 mRNA and protein may be regulated by growth factors such as 5␣-dihydrotestosterone, insulin-like growth factor I, and epidermal growth factor, known modulators of PCa cell growth and invasion.Experimental Design: ADAM-10 expression was analyzed by in situ hybridization and immunohistochemistry in prostate tissues obtained from 23 patients with prostate disease. ADAM-10 regulation was assessed using quantitative reverse transcription-PCR and Western blot analysis in the PCa cell line LNCaP.Results: ADAM-10 expression was localized to the secretory cells of prostate glands, with additional basal cell expression in benign glands. ADAM-10 protein was predominantly membrane bound in benign glands but showed marked nuclear localization in cancer glands. By Western blot, the 100-kDa proform and the 60-kDa active form of ADAM-10 were synergistically up-regulated in LNCaP cells treated with insulin-like growth factor I plus 5␣-dihydrotestosterone. Epidermal growth factor also up-regulated both ADAM-10 mRNA and protein.Conclusions: This study describes for the first time the expression, regulation, and cellular localization of ADAM-10 protein in PCa. The regulation and membrane localization of ADAM-10 support our hypothesis that ADAM-10 has a role in extracellular matrix maintenance and cell invasion, although the potential role of nuclear ADAM-10 is not yet known.

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Section: Adam-10 In Prostate Cancersupporting

confidence: 75%

Expression of the Disintegrin Metalloprotease, ADAM-10, in Prostate Cancer and Its Regulation by Dihydrotestosterone, Insulin-Like Growth Factor I, and Epidermal Growth Factor in the Prostate Cancer Cell Model LNCaP

McCulloch

Akl

Samaratunga

et al. 2004

Clinical Cancer Research

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“…Moreover, the ratio PAi-1/uPA appeared clearly in favour of PAi-1, suggesting that uPA activity might be efficiently neutralized. Recently, studies have demonstrated that EGF and AR were able to induce the expression of matrix metalloproteinases (MPPs) in a variety of tumoral cell lines (Kondapaka et al, 1997;Sundareshan et al, 1999). Although these studies have not established a direct link between the increased production of MMPS and cell invasiveness, we suggest that EGF and AR might modulate invasion of MCF-7 cells by up-regulating the expression of member(s) of MPP family.…”

Section: Discussionmentioning

confidence: 67%

Differential regulation of cell proliferation and protease secretion by epidermal growth factor and amphiregulin in tumoral versus normal breast epithelial cells

et al. 2001

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Summary Amphiregulin (AR) is a heparin-binding epidermal growth factor (EGF)-related peptide that seems to play an important role in mammary epithelial cell growth regulation. We have investigated the regulation of AR-gene expression and -protein secretion by EGF in normal breast epithelial cells (HMECs), as well as in the tumoral breast epithelial cell lines MCF-7 and MDA-MB231. EGF induced a dosedependent increase of AR mRNA level in both normal and tumoral cells. Thus, 10 Ϫ8 M EGF stimulated AR expression in HMECs to 140-300% of control. A similar EGF concentration increased AR mRNA level to 550% and 980% of control in MCF-7 and MDA-MB231 cells, respectively. This was accompanied by an accumulation of AR into conditioned culture media. However, HMECs secreted in response to EGF, 5-10 fold more AR than tumour cells. Furthermore, the potential participation of AR in the regulation of the plasminogen activator (PA)/plasmin system was investigated. Whereas HMEC-proliferation was stimulated by AR, the levels of secreted urokinase-type plasminogen activator (uPA) and type-1 plasminogen activator inhibitor (PAi-1) remained unaffected. Conversely, AR failed to regulate the proliferation of tumoral cell lines but induced an accumulation of uPA and PAi-1 into culture media. This was accompanied by an increase of the number of tumoral cells that invaded matrigel in vitro. Moreover, the presence of a neutralizing anti-uPA receptor antibody reversed the increased invasiveness of MDA-MB231 cells induced by AR. These data reveal differential behaviour of normal versus tumoral breast epithelial cells in regard to the action of AR and demonstrate that, in a number of cases, AR might play a significant role in tumour progression through the regulation of the PA/plasmin system. Whereas the expression of AR in a variety of both nontransformed and tumoral cells appears to be stimulated in the presence of EGF (Normanno et al, 1994b;Sehgal et al, 1994), the potential regulation of AR by growth factors in normal breast epithelial cells has never been examined. Because previous studies suggest that dysregulated expression of AR may be a component of mammary tumorigenesis we proposed to analyse and to compare the regulation of amphiregulin gene expression and protein secretion by EGF in normal and tumoral breast epithelial cells. Moreover, our aim was to examine potential role of AR in the regulation of uPA and PAi-1 protein secretion that could account for breast cancer progression. MATERIAL AND METHODS MaterialsAnti-smooth muscle α-actin, -actin, -vimentin and -cytokeratin 14, 18 and 19 antibodies were provided by Sigma (St Quentin Fallavier, France); Anti-vimentin antibody was from DAKO (Denmark). The AR cDNA probe was obtained from Dr. Plowman (Bristol-Myers Squibb, Seattle, WA). Matrigel was provided by Becton-Dickinson (France). Anti-uPA receptor neutralizing antibody, recombinant human AR and AR enzyme-immunoassay kit were from R & D Systems (Abingdon, UK). Antibodies used in ELISA determination of AR recognize various forms of...

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“…In the present study, we identified coexpression of the activated EGF receptor and MMP-7 by immunohistochemistry; however, one cannot determine which is dominant by an immunohistochemistry study alone. Sundareshan et al (27) have reported converse findings to ours in human prostate carcinoma cells, that regulation of matrilysin expression could not be regulated by the EGF receptor. Ueda et al (28) also reported that matrilysin secreted by a cervical carcinoma cell was not affected by EGF.…”

Section: Discussionmentioning

confidence: 99%

Coexpression of Matrix Metalloproteinase-7 (MMP-7) and Epidermal Growth Factor (EGF) Receptor in Colorectal Cancer

Mimori

Yamashita

Ohta³

et al. 2004

Clinical Cancer Research

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Purpose: Matrix metalloproteinase-7 (MMP-7) plays an important role in carcinoma invasion and metastasis of cancer. Recent studies focus on diverse roles of MMP-7, other than as a protease, during cancer progression. MMP-7 activates the epidermal growth factor (EGF) receptor by releasing an EGF ligand, tumor growth factor (TGF)-␣.Experimental Design: We examined expression of MMP-7 and EGF receptor in an immunohistochemical study of 40 colorectal cancer (CRC) cases. To determine the relationship between the EGF receptor and MMP-7, with a potential curative application, we compared the antitumor activity of the EGF receptor tyrosine kinase inhibitor (gefitinib) between MMP-7 transfectant, KYSE150 and HT29, and control cells.Results: We found a statistically significant correlation (P ‫؍‬ 0.04) between MMP-7 and activated (phosphorylated) EGF receptor expression, both being positive in six (15%) cases. Gefitinib reduced the cell number ratio more for MMP-7 transfectant than mock cells, and the proportion of apoptotic cells was 1.5 times higher in MMP-7 transfectant than mock cells by annexin/propidium iodide staining. This was mediated by activation of a TGF-␤ signal as confirmed by the abundant expression of TGF-␤ protein, the cytoplasmic to nuclear translocation of Smad4 protein by the administration of gefitinib, and the quantitative assay of the plasminogen activator inhibitor-1 promoter/luciferase construction.Conclusions: We propose that there are some cancers with up-regulated MMP-7 expression that leads to the activation of apoptotic activity of TGF-␤, which is susceptible to treatment with EGF receptor tyrosine kinase inhibitor.

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EGF induces the expression of matrilysin in the human prostate adenocarcinoma cell line, LNCaP

Cited by 21 publications

References 36 publications

Expression of the Disintegrin Metalloprotease, ADAM-10, in Prostate Cancer and Its Regulation by Dihydrotestosterone, Insulin-Like Growth Factor I, and Epidermal Growth Factor in the Prostate Cancer Cell Model LNCaP

Expression of the Disintegrin Metalloprotease, ADAM-10, in Prostate Cancer and Its Regulation by Dihydrotestosterone, Insulin-Like Growth Factor I, and Epidermal Growth Factor in the Prostate Cancer Cell Model LNCaP

Differential regulation of cell proliferation and protease secretion by epidermal growth factor and amphiregulin in tumoral versus normal breast epithelial cells

Coexpression of Matrix Metalloproteinase-7 (MMP-7) and Epidermal Growth Factor (EGF) Receptor in Colorectal Cancer

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