Abstract
Store-operated Ca2+ entry (SOCE) is activated following depletion of the inositol-1,4,5-trisphosphate (InsP3)-sensitive Ca2+ pool to regulate proliferation in immortalized cell lines established from either primary or metastatic lesions. The molecular nature of SOCE may involve both Stim1, which senses Ca2+ levels within the endoplasmic reticulum (ER) Ca2+ reservoir, and a number of a Ca 2+-permeable channels on the plasma membrane, including Orai1, Orai3, and members of the canonical transient receptor (TRPC1-7) family of ion channels. The present study was undertaken to assess whether SOCE is expressed and controls proliferation in primary cultures isolated from secondary lesions of heavily pretreated metastatic renal cell carcinoma (mRCC) patients. SOCE was induced following pharmacological depletion of the ER Ca2+ store, but not by InsP3-dependent Ca2+ release. Metastatic RCC cells express Stim1-2, Orai1-3, and TRPC1-7 transcripts and proteins. In these cells, SOCE was insensitive to BTP-2, 10 μM Gd3+ and Pyr6, while it was inhibited by 100 μM Gd3+, 2-APB, and carboxyamidotriazole (CAI). Neither Gd3+ nor 2-APB or CAI impaired mRCC cell proliferation. Consistently, no detectable Ca2+ signal was elicited by growth factor stimulation. Therefore, a functional SOCE is expressed but does not control proliferation of mRCC cells isolated from patients resistant to multikinase inhibitors.
| Original language | English |
|---|---|
| Article number | 739494 |
| Journal | BioMed Research International |
| Volume | 2014 |
| DOIs | |
| Publication status | Published - 2014 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
- Medicine(all)
Cite this
Store-operated Ca2+ entry does not control proliferation in primary cultures of human metastatic renal cellular carcinoma. / Dragoni, Silvia; Turin, Ilaria; Laforenza, Umberto; Potenza, Duilio Michele; Bottino, Cinzia; Glasnov, Toma N.; Prestia, Martina; Ferulli, Federica; Saitta, Anna; Mosca, Alessandra; Guerra, Germano; Rosti, Vittorio; Luinetti, Ombretta; Ganini, Carlo; Porta, Camillo; Pedrazzoli, Paolo; Tanzi, Franco; Montagna, Daniela; Moccia, Francesco.
In: BioMed Research International, Vol. 2014, 739494, 2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Store-operated Ca2+ entry does not control proliferation in primary cultures of human metastatic renal cellular carcinoma
AU - Dragoni, Silvia
AU - Turin, Ilaria
AU - Laforenza, Umberto
AU - Potenza, Duilio Michele
AU - Bottino, Cinzia
AU - Glasnov, Toma N.
AU - Prestia, Martina
AU - Ferulli, Federica
AU - Saitta, Anna
AU - Mosca, Alessandra
AU - Guerra, Germano
AU - Rosti, Vittorio
AU - Luinetti, Ombretta
AU - Ganini, Carlo
AU - Porta, Camillo
AU - Pedrazzoli, Paolo
AU - Tanzi, Franco
AU - Montagna, Daniela
AU - Moccia, Francesco
PY - 2014
Y1 - 2014
N2 - Store-operated Ca2+ entry (SOCE) is activated following depletion of the inositol-1,4,5-trisphosphate (InsP3)-sensitive Ca2+ pool to regulate proliferation in immortalized cell lines established from either primary or metastatic lesions. The molecular nature of SOCE may involve both Stim1, which senses Ca2+ levels within the endoplasmic reticulum (ER) Ca2+ reservoir, and a number of a Ca 2+-permeable channels on the plasma membrane, including Orai1, Orai3, and members of the canonical transient receptor (TRPC1-7) family of ion channels. The present study was undertaken to assess whether SOCE is expressed and controls proliferation in primary cultures isolated from secondary lesions of heavily pretreated metastatic renal cell carcinoma (mRCC) patients. SOCE was induced following pharmacological depletion of the ER Ca2+ store, but not by InsP3-dependent Ca2+ release. Metastatic RCC cells express Stim1-2, Orai1-3, and TRPC1-7 transcripts and proteins. In these cells, SOCE was insensitive to BTP-2, 10 μM Gd3+ and Pyr6, while it was inhibited by 100 μM Gd3+, 2-APB, and carboxyamidotriazole (CAI). Neither Gd3+ nor 2-APB or CAI impaired mRCC cell proliferation. Consistently, no detectable Ca2+ signal was elicited by growth factor stimulation. Therefore, a functional SOCE is expressed but does not control proliferation of mRCC cells isolated from patients resistant to multikinase inhibitors.
AB - Store-operated Ca2+ entry (SOCE) is activated following depletion of the inositol-1,4,5-trisphosphate (InsP3)-sensitive Ca2+ pool to regulate proliferation in immortalized cell lines established from either primary or metastatic lesions. The molecular nature of SOCE may involve both Stim1, which senses Ca2+ levels within the endoplasmic reticulum (ER) Ca2+ reservoir, and a number of a Ca 2+-permeable channels on the plasma membrane, including Orai1, Orai3, and members of the canonical transient receptor (TRPC1-7) family of ion channels. The present study was undertaken to assess whether SOCE is expressed and controls proliferation in primary cultures isolated from secondary lesions of heavily pretreated metastatic renal cell carcinoma (mRCC) patients. SOCE was induced following pharmacological depletion of the ER Ca2+ store, but not by InsP3-dependent Ca2+ release. Metastatic RCC cells express Stim1-2, Orai1-3, and TRPC1-7 transcripts and proteins. In these cells, SOCE was insensitive to BTP-2, 10 μM Gd3+ and Pyr6, while it was inhibited by 100 μM Gd3+, 2-APB, and carboxyamidotriazole (CAI). Neither Gd3+ nor 2-APB or CAI impaired mRCC cell proliferation. Consistently, no detectable Ca2+ signal was elicited by growth factor stimulation. Therefore, a functional SOCE is expressed but does not control proliferation of mRCC cells isolated from patients resistant to multikinase inhibitors.
UR - http://www.scopus.com/inward/record.url?scp=84904818123&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904818123&partnerID=8YFLogxK
U2 - 10.1155/2014/739494
DO - 10.1155/2014/739494
M3 - Article
C2 - 25126575
AN - SCOPUS:84904818123
VL - 2014
JO - BioMed Research International
JF - BioMed Research International
SN - 2314-6133
M1 - 739494
ER -