title: Decreased DAB2IP gene expression, which could be induced by fractionated irradiation, is associated with resistance to γ‑rays and α‑particles in prostate cancer cells.
abstract: External beam radiation therapy, alone or combined with androgen deprivation, is a well‑established treatment for prostate cancer (PCa). However, not all patients benefit from radiotherapy due to congenital or acquired radioresistance. The preliminary results of the present study indicated that the loss of disabled homolog 2 interactive protein (DAB2IP) expression in PCa and normal prostate epithelia results in the resistance to γ‑rays. To further explore the association between DAB2IP and ionizing radiation (IR), PCa cells were fractionally irradiated 12 times with 2 Gy of γ‑rays and the change in DAB2IP mRNA expression was monitored. Notably, along with a continuous reduction of DAB2IP expression levels, increased expression levels of ataxia‑telangiectasia mutated (ATM) was observed in IR‑treated cells. In order to improve the sensitivity of DAB2IP‑deficient cells to IR, α‑particles, a type of high linear energy transfer radiation and KU55933, an ATM inhibitor, were used in the current study. It was determined that α‑particle irradiations were more effective than γ‑rays on cells expressing expected and decreased levels of DAB2IP. However, cells with a dysfunctional DAB2IP gene were resistant to α‑particle irradiation. Treatment with KU55933 did not enhance cell sensitivity to α‑irradiation. Therefore, this suggested that DAB2IP downregulation induced by radiotherapy may be associated with acquired radioresistance in patients with PCa.
authors.affiliation: Department of Radiobiology, The Institute of Radiation Medicine, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Radiobiology, The Institute of Radiation Medicine, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Radiobiology, The Institute of Radiation Medicine, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Division of Children's Health, Huai'an Women and Children Hospital, Huai'an, Jiangsu 223002, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Radiobiology, The Institute of Radiation Medicine, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Zhaolu
authors.initials: Z
authors.lastname: Kong
mesh_terms: D000512:Alpha Particles; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D000070818:Discoidin Domain Receptors / Q000378:metabolism; D005720:Gamma Rays; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy; D011753:Pyrones / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics*; D015398:Signal Transduction / Q000528:radiation effects; D020703:ras GTPase-Activating Proteins / Q000235:genetics*
chemical_list: C495818:2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one; C462952:DAB2IP protein, human; D009025:Morpholines; D011753:Pyrones; D012333:RNA, Messenger; D020703:ras GTPase-Activating Proteins; D000070818:Discoidin Domain Receptors