Isolation and molecular cloning of human sorcin a calcium-binding protein in vincristine-resistant H0B1 lymphoma cells

Wang, Sung-Ling; Tam, Ming-F.; Ho, Yat‐Sen; Pai, S. H.; Kao, Ming‐Ching

doi:10.1016/0167-4781(94)00206-i

Cited by 24 publications

(17 citation statements)

References 35 publications

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“…Some evidence suggests that sorcin may be responsible for inducing MDR in human tumors (17)(18)(19)(20)(21)(22)(23), but no information is available on the specific function of the 22 kDa isoform in CRC drug resistance. Thus, pRC-or 22 kDa sorcin-HCT-116-stable transfectants ( Supplementary Fig.…”

Section: The 22 Kda Isoform Of Sorcin Is Involved In Mdr In Human Crcmentioning

confidence: 99%

“…Because the above studies suggest an involvement of the 22 kDa sorcin isoform in the cytoprotective pathways of human cancer cells (17)(18)(19)(20)(21)(22)(23), without providing a more in-depth explanation of its function, and considering that we previously showed that only the mitochondrial isoform of sorcin interacts with TRAP1 and is crucial for its antiapoptotic function (11), we became interested in studying the expression of 22 kDa sorcin in human CRC and in characterizing its role in the drugresistant phenotype of this malignancy.…”

Section: Introductionmentioning

confidence: 99%

“…Some evidence suggests involvement of sorcin in the drug resistance shown by human malignancies. Indeed, sorcin was purified from a vincristine-resistant lymphoma cell line (17), whereas its overexpression has also been associated with resistance to vincristine in gastric cancer cells (18), gemcitabine in non-small cell lung cancer (NSCLC; ref. 19) and CHOP regimen in diffuse large B-cell lymphoma (20).…”

Section: Introductionmentioning

confidence: 99%

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Sorcin Induces a Drug-Resistant Phenotype in Human Colorectal Cancer by Modulating Ca2+ Homeostasis

et al. 2011

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The Ca 2þ -binding protein sorcin regulates intracellular calcium homeostasis and plays a role in the induction of drug resistance in human cancers. Recently, an 18 kDa mitochondrial isoform of sorcin was reported to participate in antiapoptosis in human colorectal cancer (CRC), but information remains lacking about the functional role of the more abundant 22 kDa isoform of sorcin expressed in CRC. We found the 22 kDa isoform to be widely expressed in human CRC cells, whether or not they were drug resistant. Its upregulation in drugsensitive cells induced resistance to 5-fluorouracil, oxaliplatin, and irinotecan, whereas its downregulation sensitized CRC cells to these chemotherapeutic agents. Sorcin enhances the accumulation of Ca 2þ in the endoplasmic reticulum (ER), preventing ER stress, and, in support of this function, we found that the 22 kDa isoform of sorcin was upregulated under conditions of ER stress. In contrast, RNAi-mediated silencing of sorcin activated caspase-3, caspase-12, and GRP78/BiP, triggering apoptosis through the mitochondrial pathway. Our findings establish that CRC cells overexpress sorcin as an adaptive mechanism to prevent ER stress and escape apoptosis triggered by chemotherapeutic agents, prompting its further investigation as a novel molecular target to overcome MDR. Cancer Res; 71(24); 7659-69. Ó2011 AACR.

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Section: The 22 Kda Isoform Of Sorcin Is Involved In Mdr In Human Crcmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sorcin Induces a Drug-Resistant Phenotype in Human Colorectal Cancer by Modulating Ca2+ Homeostasis

et al. 2011

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“…However, to date, the contribution of sorcin to the MDR phenomenon has been questionable. Studies on VCR-resistant HOB1 lymphoma cell lines revealed that the sorcin gene was amplified upon exposure of parental HOB1 cells to a high concentration of VCR, and this phenomenon was not related to MDR1 gene amplification in the drugresistant cells (22,23). Kawakami et al (24) reported that suppressing of MDR1 expression with siRNA did not change the expression level of sorcin mRNA, whereas the knockdown of sorcin induced up-regulation of MDR1 mRNA in HeLa cells.…”

Section: Discussionmentioning

confidence: 99%

“…The overexpression of sorcin genes may just be coincidental with the amplification of MDR (21). Other conflicting results suggested that sorcin might be independently involved in mediating MDR (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of sorcin results in multidrug resistance in gastric cancer cells with up-regulation of P-gp

Zhang²,

Hou³

et al. 2010

Oncol Rep

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Abstract. Sorcin, a calcium-binding protein was found upregulated in the vincristine-induced multi-drug resistance (MDR) gastric cancer cell line SGC7901/VCR, over its parental SGC7901 cells in our previous proteomic studies. The present study explored the role and mechanism of sorcin in the development of MDR in gastric cancer. We constructed the recombinant plasmids FLAG-sorsin-pcDNA3.1 containing the full open reading frame of sorcin and a FLAG affinity tag. Overexpression of sorcin by gene transfection was able to confer drug resistance to vincristine, adriamycin, taxol and 5-fluorouracil in SGC7901 cells.Down-regulation of sorcin expression by sorcin antisense oligonucleutides, (ASO) increased sensitivity to vincristine. The intracellular concentration of vincristine in SGC7901 cells decreased in sorcintransfected cells and increased in sorcin ASO-transfected cells, indicating that sorcin had a direct or indirect function on pumping the drug out of cells. Overexpression of sorcin up-regulated the expression of P-gp and P-gp inhibitor verapamil partially reversed the sorcin-mediated MDR in SGC7901 cell, suggesting that regulation of P-gp might be one of the mechanisms of sorcin-mediated MDR. The further study of the interaction protein of sorcin may be helpful for understanding the mechanisms of MDR in gastric cancer and developing possible strategies to treat gastric cancer.

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PEFLINS: A Family of PentaEF‐Hand Proteins

Cygler

2004

Handbook of Metalloproteins

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Penta‐EF hand proteins, or PEFLINs, belong to the superfamily of regulatory Ca 2+ ‐binding proteins with EF‐hand motifs. The calcium‐binding domain is ∼170 residues long and contains five EF‐hand motifs, of which only some retain the ability to bind calcium. Within individual molecules the (1st + 2nd) and (3rd + 4th) EF‐hands are associated in pairs while the 5th EF‐hand is unpaired. This domain is associated with an N‐terminal domain of varying length, usually 20 to 100 residues long and with a Gly/Pro‐rich region. Binding of Ca 2+ promotes association of these proteins with membranes, and in vitro leads to aggregation. On the basis of the 1st EF‐hand, these proteins are divided into two subfamilies. Calpain, grancalcin, and sorcin have a one‐residue deletion in the Ca 2+ ‐binding loop between helices E and F and form a distinct variant of calcium binding. ALG‐2 and peflin have the canonical EF1 hand and bind calcium in a standard way. All penta‐EF hand proteins form homo‐ or heterodimers. The dimerization is promoted by pairing of the 5th EF‐hand of each molecule; thus in the dimer all EF‐hands are paired. Binding of Ca 2+ promotes only small, mostly local, conformational changes and it is plausible that binding of a concomitant partner molecule is required for larger rearrangements to occur.

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Isolation and molecular cloning of human sorcin a calcium-binding protein in vincristine-resistant H0B1 lymphoma cells

Cited by 24 publications

References 35 publications

Sorcin Induces a Drug-Resistant Phenotype in Human Colorectal Cancer by Modulating Ca2+ Homeostasis

Sorcin Induces a Drug-Resistant Phenotype in Human Colorectal Cancer by Modulating Ca2+ Homeostasis

Overexpression of sorcin results in multidrug resistance in gastric cancer cells with up-regulation of P-gp

PEFLINS: A Family of PentaEF‐Hand Proteins

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