The radiation response of androgen-refractory prostate cancer cell line C4-2 derived from androgen-sensitive cell line LNCaP

Abstract

Radiation therapy is a relatively effective therapeutic method for localized prostate cancer (PCa) patients. However, radioresistance occurs in nearly 30% of patients treated with potentially curative doses. Therapeutic synergy between radiotherapy and androgen ablation treatment provides a promising strategy for improving the clinical outcome. Accordingly, the androgen deprivation-induced signaling pathway may also mediate radiosensitivity in PCa cells. The C4-2 cell line was derived from the androgen-sensitive LNCaP parent line under androgen-depleted condition and had acquired androgen-refractory characteristics. In our study, the response to radiation was evaluated in both LNCaP and C4-2. Results showed that C4-2 cells were more likely to survive from irradiation and appeared more aggressive in their resistance to radiation treatment compared with LNCaP, as measured by clonogenic assays and cell viability and cell cycle analyses. Gene expression analyses revealed that a set of genes involved in cell cycle arrest and DNA repair were differentially regulated in LNCaP and C4-2 in response to radiation, which was also consistent with the radiation-resistant property observed in C4-2 cells. These results strongly suggested that the radiation-resistant property may develop with progression of PCa to androgen-independent status. Not only can the LNCaP and C4-2 PCa progression model be applied for investigating androgen-refractory progression, but it can also be used to explore the development of radiation resistance in PCa.

Linc00963: A novel, long non-coding RNA involved in the transition of prostate cancer from androgen-dependence to androgen-independence

“…The prostate cancer cell line C4-2 acquires the phenotypes of androgenindependence and osseous metastases, and it is commonly used in models of castration-resistant and aggressive prostate cancer (22). The second part of our study identified the role of Linc00963 in AI prostate cancer cells.…”

“…Prostate cancer cell line LNCaP and C4-2 have the same genetic background and the unique advantage of remarkably mimicking the phenotypic and genotypic changes observed in clinical human PCa (22). In the current study, we used microarray technology to compare the lncRNA and mRNA expression between LNCaP cell line which was an androgen-dependent, non-metastasis (23) and the lineage-related C4-2 cell line which acquired characteristic of androgen-independence and possessed the capacity of metastasizing to lymph nodes and bone (24).…”

Evaluation of the radiosensitizing potency of chemotherapeutic agents in prostate cancer cells

“…In PC3 cells, the cell cycle distribution returns to control proportions 24 h after irradiation, whereas LNCaP cells accumulate in G 1 phase. This may be explained by the inefficiency of DNA damage repair mechanisms reported in LNCaP cells in G 2 /M phase (Xie et al 2010) and consequent reliance of G 1 checkpoints, whereas PC3 cells lack the ability to arrest in G 1 phase.…”

Annexin A2 and S100A10 Regulate Human Papillomavirus Type 16 Entry and Intracellular Trafficking in Human Keratinocytes

“…C4-2 prostate adenocarcinoma cells are derivatives from the LNCaP epithelial cell line, which lacks AnxA2 expression due to the hypermethylation of the AnxA2 promoter (65,66). They were gifts from G. N. Thalmann (University of Bern) and were maintained as reported previously (67). HPV16 pseudovirions (PsVs) encapsidating a luciferase expression plasmid were generated and purified as described previously (63,68,69).…”