May 15, 2008

ASNA1, an ATPase targeting tail-anchored proteins, regulates melanoma cell growth and sensitivity to cisplatin and arsenite

Cancer Chemotherapy and Pharmacology
O HemmingssonP Naredi

Abstract

ASNA1 is homologous to E. coli ArsA, a well characterized ATPase involved in efflux of arsenite and antimonite. Cells resistant to arsenite and antimonite are cross-resistant to the chemotherapeutic drug cisplatin. ASNA1 is also an essential ATPase for the insertion of tail-anchored proteins into ER membranes and a novel regulator of insulin secretion. The aim of this study was to determine if altered ASNA1 levels influenced growth and sensitivity to arsenite and cisplatin in human melanoma cells. Cultured melanoma T289 cells were transfected with plasmids containing sense or antisense ASNA1. Cells were exposed to cisplatin, arsenite and zinc. Cell growth and chemosensitivity were evaluated by the MTT assay and apoptosis by a TUNEL assay. ASNA1 expression was necessary for growth. T289 clones with decreased ASNA1 expression exhibited 51 +/- 5% longer doubling times than wildtype T289 (P = 0.0091). After exposure to cisplatin, ASNA1 downregulated cells displayed a significant increase in apoptosis. The cisplatin IC(50) in ASNA1 underexpressing cells was 41.7 +/- 1.8% compared to wildtype (P = 0.00097) and the arsenite IC(50) was 59.9 +/- 3.2% of wildtype IC(50) (P = 0.0067). Reduced ASNA1 expression is associated with significan...Continue Reading

  • References20
  • Citations9

Citations

Mentioned in this Paper

ASNA1 gene
Tissue Membrane
Apoptosis, Intrinsic Pathway
Adenosine Triphosphatases
Immunocytochemistry
ASNA1 protein, human
Arsenite
Melanoma vaccine
Western Blot
Cell Growth

Related Feeds

Antisense Oligonucleotide - Therapies For ALS

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis