Association of c-myc Overexpression and Hyperproliferation with Arsenite-Induced Malignant Transformation

Sodium arsenite-induced stress-related gene expression in normal human epidermal, HaCaT, and HEL30 keratinocytes.

“…However, the elevated baseline stk25 expresssion observed in HaCaT and HEL30 keratinocytes would support the notion that this alteration is associated with immortalization. Along with previously defined effects of arsenic on mitogen and stress-related signal transduction (7,10,16,33,59), these data implicate STK25 in the transduction of arsenite-mediated stress signals.…”

“…Mechanisms proposed to be involved in the development of arsenic-induced cancer in skin and other tissues include altered DNA methylation (10)(11)(12), DNA repair/ replication disturbances (13,14), clastogenicity and aneuploidy (15), dysregulated cell proliferation (10,16), and generation of oxidative stress (17,18). Arsenic-induced oxidative stress or redox disturbance (17,(19)(20)(21) contributes to DNA damage (22)(23)(24), chromosomal aberrations (25), and protein expression alterations (22,26).…”

Cadmium‐induced malignant transformation in rat liver cells: Role of aberrant oncogene expression and minimal role of oxidative stress

“…20 In addition, c-myc can also be transforming by simple overexpression, 37 and its overexpression would be consistent with enhanced mitogenic activity. 38 It seems that the overexpression of these oncogenes, without an obligate mutation, may be sufficient to initiate cadmium-induced malignant transformation.…”

Long term low-dose arsenic exposure induces loss of DNA methylation

“…cDNA was synthesized by reverse transcription of 1 μg total RNA in a total volume of 20 μl containing 1X reverse transcriptase buffer (Invitrogen), 25 μg/ml oligo (dT) [12][13][14][15][16][17][18] (Invitrogen), 0.5 mM dNTP mix (GeneChoice), 10 mM dithiothreitol (Invitrogen), 20 U of RNase inhibitor (RNasin®, Promega), and 100 U of SuperScript™ II reverse transcriptase (Invitrogen). Samples were denatured and annealed to the (dT) [12][13][14][15][16][17][18] deoxyribonucleotide primer for 10 min at 70°C, and reverse-transcribed for 1 h at 42ºC. Before amplification, the reverse transcriptase was inactivated by heating to 70ºC for 15 min, and RNA was hydrolyzed by incubation with 2 U RNase H (Invitrogen) at 37°C for 20 min.…”