[Expression of P53, NPM1, Kras, c-Myc, p14(ARF) genes in blood cells of cancer patients before and after radiation therapy]

Radiats Biol Radioecol. 2012 Nov-Dec;52(6):572-81.
[Article in Russian]

Abstract

The mRNA levels of P53gene, as well as NPM1, Kras, c-Myc, p14(ARF) genes, which, according to the published data, code for the proteins regulating the p53 activity, were studied using RT-PCR method in blood cells of patients with different localization of tumor process (prostate cancer, breast cancer and head and neck cancer) before and after application of radiation therapy. Changes in gene expression of cancer patients were compared with the control group of healthy donors. We have established that all patients had a decreased level of the Kras gene expression even before radiotherapy; moreover, the group of patients with prostate cancer had a low content of mRNA in NPM1 and p14(ARF), and the group of patients with head and neck cancerhad a reliably reduced mRNA in P53, NPM1 and p14(ARF). The radiation therapy did not cause essential changes in the expression of these genes of cancer patients, ecpect for the Kras gene, whose the mRNA level in the group of patients with head and neck cancer was reliably lower than the mRNA level prior to beginning of radiation therapy. The correlations of P53, NPM1, Kras, p14(ARF) gene expression were studied. We have shown that p14(ARF) mRNA level negatively correlates with Kras mRNA (R = -0.6, p = 0.002) and P53 mRNA levels (R = -0.49, p = 0.013) in the control group of healthy donors. A positive correlation was observed between P53 mRNA and NPM1 mRNA (R = 0.54, p = 0.006). Similar correlations between mRNA levels of these genes in blood cells were absent in the cancer patients before radiotherapy. After radiotherapy in patients with prostate cancer, p14(ARF) mRNA level positively correlated with NPM1 mRNA (R = 0.7, p = 0.001) and negatively with Kras mRNA (R = - 0.5, p = 0.03). Our results provide evidence that expression P53, NPM1, Kras and p14(ARF) genes may be coordinated in blood cells of healthy donors. The low expression levels of the studied genes in patients can contribute to the increase in the mutation changes in blood cells of the examined subjects after the action of genotoxic factors.

MeSH terms

  • ADP-Ribosylation Factor 1 / blood
  • Female
  • Gene Expression Regulation, Neoplastic / radiation effects*
  • Humans
  • Male
  • Middle Aged
  • Neoplasms* / blood
  • Neoplasms* / genetics
  • Neoplasms* / radiotherapy
  • Nuclear Proteins / blood
  • Nucleophosmin
  • Proto-Oncogene Proteins / blood
  • Proto-Oncogene Proteins c-myc / blood
  • Proto-Oncogene Proteins p21(ras)
  • Tumor Suppressor Protein p53 / blood
  • ras Proteins / blood

Substances

  • KRAS protein, human
  • NPM1 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Nucleophosmin
  • ADP-Ribosylation Factor 1
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins