The functional effects of acid ceramidase overexpression in prostate cancer progression and resistance to chemotherapy
Among the many processes regulating cell death, ceramide signaling is a vital component. We previously determined that acid ceramidase (AC) is upregulated in 60% of primary prostate cancer (PCa) tissues, suggesting that AC may play a role in tumor development. In order to determine the significance of AC elevation, stable clones of DU145 cells with AC overexpression (AC-EGFP) were generated. Compared to controls (EGFP), AC-EGFP cells exhibited enhanced cell proliferation and migration. Subcutaneous injection of AC-EGFP cells into Nu/Nu mice resulted in larger tumor volumes compared to EGFP controls. Moreover, using the MTS viability assay, AC-EGFP cells were more resistant to cell death induced by doxorubicin, cisplatin, etoposide, gemcitabine or C6-ceramide. Conversely, knock down of AC using siRNA, sensitized AC-EGFP cells to these drugs. In addition, mass spectroscopic analysis of sphingolipids indicated that long chain ceramide levels were decreased in AC-EGFP cells treated with either doxorubicin or etoposide. In conclusion, this study implicates AC as a critical regulator of PCa progression by affecting not only tumor cell proliferation and migration but also responses to drug therapy, suggesting AC as a potential therapeutic target in advanced PCa.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2007 |
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| Erschienen: |
2007 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
|---|---|
| Enthalten in: |
Cancer biology & therapy - 6(2007), 9 vom: 15. Sept., Seite 1455-60 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Saad, Antonio F [VerfasserIn] |
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| Themen: |
038753E78J |
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| Anmerkungen: |
Date Completed 28.05.2008 Date Revised 30.09.2020 published: Print-Electronic Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM173882536 |
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| 100 | 1 | |a Saad, Antonio F |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The functional effects of acid ceramidase overexpression in prostate cancer progression and resistance to chemotherapy |
| 264 | 1 | |c 2007 | |
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| 500 | |a Date Completed 28.05.2008 | ||
| 500 | |a Date Revised 30.09.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Among the many processes regulating cell death, ceramide signaling is a vital component. We previously determined that acid ceramidase (AC) is upregulated in 60% of primary prostate cancer (PCa) tissues, suggesting that AC may play a role in tumor development. In order to determine the significance of AC elevation, stable clones of DU145 cells with AC overexpression (AC-EGFP) were generated. Compared to controls (EGFP), AC-EGFP cells exhibited enhanced cell proliferation and migration. Subcutaneous injection of AC-EGFP cells into Nu/Nu mice resulted in larger tumor volumes compared to EGFP controls. Moreover, using the MTS viability assay, AC-EGFP cells were more resistant to cell death induced by doxorubicin, cisplatin, etoposide, gemcitabine or C6-ceramide. Conversely, knock down of AC using siRNA, sensitized AC-EGFP cells to these drugs. In addition, mass spectroscopic analysis of sphingolipids indicated that long chain ceramide levels were decreased in AC-EGFP cells treated with either doxorubicin or etoposide. In conclusion, this study implicates AC as a critical regulator of PCa progression by affecting not only tumor cell proliferation and migration but also responses to drug therapy, suggesting AC as a potential therapeutic target in advanced PCa | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Meacham, William D |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Aiping |e verfasserin |4 aut | |
| 700 | 1 | |a Anelli, Viviane |e verfasserin |4 aut | |
| 700 | 1 | |a Elojeimy, Saeed |e verfasserin |4 aut | |
| 700 | 1 | |a Mahdy, Ayman E M |e verfasserin |4 aut | |
| 700 | 1 | |a Turner, Lorianne S |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Joe |e verfasserin |4 aut | |
| 700 | 1 | |a Bielawska, Alicja |e verfasserin |4 aut | |
| 700 | 1 | |a Bielawski, Jacek |e verfasserin |4 aut | |
| 700 | 1 | |a Keane, Thomas E |e verfasserin |4 aut | |
| 700 | 1 | |a Obeid, Lina M |e verfasserin |4 aut | |
| 700 | 1 | |a Hannun, Yusuf A |e verfasserin |4 aut | |
| 700 | 1 | |a Norris, James S |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiang |e verfasserin |4 aut | |
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