Aggressive melanoma cells escape from BMP7-mediated autocrine growth inhibition through coordinated Noggin upregulation
Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily responsible for mediating a diverse array of cellular functions both during embryogenesis and in adult life. Previously, we reported that upregulation of BMP7 in human melanoma correlates with tumor progression. However, melanoma cells are either inhibited by or become resistant to BMP7 as a function of tumor progression, with normal melanocytes being most susceptible. Herein, real-time quantitative reverse transcriptase-polymerase chain reactions and western blotting revealed that the expression of BMP antagonist, Noggin, correlates with resistance to BMP7 in advanced melanoma cells. To test the hypothesis that coordinated upregulation of Noggin protects advanced melanoma cells from autocrine inhibition by BMP7, functional expression of Noggin in susceptible melanoma cells was achieved by adenoviral gene transfer. The Noggin-overexpressing cells exhibited a growth advantage in response to subsequent BMP7 transduction in vitro under anchorage-dependent and -independent conditions, in three-dimensional skin reconstructs, as well as in vivo in severe combined immunodeficient mice. In concordance, Noggin knockdown by lentiviral shRNA confers sensitivity to BMP7-induced growth inhibition in advanced melanoma cells. Our findings suggest that, like TGF-beta, BMP7 acts as an autocrine growth inhibitor in melanocytic cells, and that advanced melanoma cells may escape from BMP7-induced inhibition through concomitant aberrant expression of Noggin.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2008 |
|---|---|
| Erschienen: |
2008 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:88 |
|---|---|
| Enthalten in: |
Laboratory investigation; a journal of technical methods and pathology - 88(2008), 8 vom: 02. Aug., Seite 842-55 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hsu, Mei-Yu [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 21.08.2008 Date Revised 05.11.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/labinvest.2008.55 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM180274988 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM180274988 | ||
| 003 | DE-627 | ||
| 005 | 20231223155212.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231223s2008 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/labinvest.2008.55 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0601.xml |
| 035 | |a (DE-627)NLM180274988 | ||
| 035 | |a (NLM)18560367 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hsu, Mei-Yu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Aggressive melanoma cells escape from BMP7-mediated autocrine growth inhibition through coordinated Noggin upregulation |
| 264 | 1 | |c 2008 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 21.08.2008 | ||
| 500 | |a Date Revised 05.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily responsible for mediating a diverse array of cellular functions both during embryogenesis and in adult life. Previously, we reported that upregulation of BMP7 in human melanoma correlates with tumor progression. However, melanoma cells are either inhibited by or become resistant to BMP7 as a function of tumor progression, with normal melanocytes being most susceptible. Herein, real-time quantitative reverse transcriptase-polymerase chain reactions and western blotting revealed that the expression of BMP antagonist, Noggin, correlates with resistance to BMP7 in advanced melanoma cells. To test the hypothesis that coordinated upregulation of Noggin protects advanced melanoma cells from autocrine inhibition by BMP7, functional expression of Noggin in susceptible melanoma cells was achieved by adenoviral gene transfer. The Noggin-overexpressing cells exhibited a growth advantage in response to subsequent BMP7 transduction in vitro under anchorage-dependent and -independent conditions, in three-dimensional skin reconstructs, as well as in vivo in severe combined immunodeficient mice. In concordance, Noggin knockdown by lentiviral shRNA confers sensitivity to BMP7-induced growth inhibition in advanced melanoma cells. Our findings suggest that, like TGF-beta, BMP7 acts as an autocrine growth inhibitor in melanocytic cells, and that advanced melanoma cells may escape from BMP7-induced inhibition through concomitant aberrant expression of Noggin | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a BMP7 protein, human |2 NLM | |
| 650 | 7 | |a Bone Morphogenetic Protein 7 |2 NLM | |
| 650 | 7 | |a Bone Morphogenetic Proteins |2 NLM | |
| 650 | 7 | |a Carrier Proteins |2 NLM | |
| 650 | 7 | |a Growth Inhibitors |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta |2 NLM | |
| 650 | 7 | |a noggin protein |2 NLM | |
| 650 | 7 | |a 148294-77-3 |2 NLM | |
| 700 | 1 | |a Rovinsky, Sherry A |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Chiou-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Qasem, Shadi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiaoming |e verfasserin |4 aut | |
| 700 | 1 | |a How, Joan |e verfasserin |4 aut | |
| 700 | 1 | |a Engelhardt, John F |e verfasserin |4 aut | |
| 700 | 1 | |a Murphy, George F |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Laboratory investigation; a journal of technical methods and pathology |d 1952 |g 88(2008), 8 vom: 02. Aug., Seite 842-55 |w (DE-627)NLM000052604 |x 1530-0307 |7 nnns |
| 773 | 1 | 8 | |g volume:88 |g year:2008 |g number:8 |g day:02 |g month:08 |g pages:842-55 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/labinvest.2008.55 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 88 |j 2008 |e 8 |b 02 |c 08 |h 842-55 | ||