title: Effect of ionizing radiation on acinar morphogenesis of human prostatic epithelial cells under three-dimensional culture conditions.
abstract: Homeostasis is maintained by the interplay of multiple factors that directly or indirectly regulate cell proliferation and cell death. Complex multiple interactions between cells and the extracellular matrix occur during acinar morphogenesis and changes in these might indicate carcinogenesis of cells from a normal to a malignant, invasive phenotype. In this study, the human prostatic epithelial cell line RWPE-1 was cultured under three-dimensional (3-D) culture conditions, and the effect of ionizing radiation on acinar morphogenesis and its association with autophagy were discussed. The results illustrated that formation of specific spheroid (acinar) structures was detectable under 3-D culture conditions. Radiation induced the disruption of acini in different cell models using either gene overexpression (Akt) or gene knock-down (Beclin 1 and ATG7). Introduction of Akt not only accelerated the growth of cells (i.e., caused the cells to manifest elongating and microspike-like structures that are obviously different from structures seen in wild-type RWPE-1 cells under two-dimensional conditions), but also changed their morphological characteristics under 3-D culture conditions. Knock-down of autophagy-related genes (Beclin 1 and ATG7) increased the radiosensitivity of cells under 3-D culture conditions, and cells died of non-apoptotic death after radiation. The results suggested that ionizing radiation may change the cell phenotype and the formation of acini. Additionally even the autophagy mechanism may play a role in these processes.
authors.affiliation: Dept. Radiation Oncology, 2nd Hospital affiliated to Jilin University, Changchun, China.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: S Ma
authors.initials: SM
authors.lastname: X
authors.forename: D
authors.initials: D
authors.lastname: Kong
authors.forename: H
authors.initials: H
authors.lastname: Yi
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Liang
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.forename: M
authors.initials: M
authors.lastname: He
authors.forename: L
authors.initials: L
authors.lastname: Jia
authors.forename: A B
authors.initials: AB
authors.lastname: Qased
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: X
authors.initials: X
authors.lastname: Liu
mesh_terms: D061354:Acinar Cells / Q000528:radiation effects*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000528:radiation effects; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002453:Cell Cycle; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis / Q000528:radiation effects*; D011467:Prostate / Q000254:growth & development* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011839:Radiation, Ionizing; D044764:Ubiquitin-Activating Enzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes