Analysis of Differentially Expressed Genes in LNCaP Prostate Cancer Progression Model

Abstract

The LNCaP/C4-2 human prostate cancer progression model was established to mimic phenotypic and genotypic changes during prostate cancer development from androgen dependence to androgen independence, from nonmetastasis to metastasis. In this study, cDNA microarrays were performed using a microarray chip from Affymetrix to characterize and compare gene expression profiles in LNCaP and C4-2, which may provide novel insight into the molecular mechanism mediating prostate cancer progression. Three hundred eighteen genes consistently exhibited differential expression in LNCaP and C4-2 in 2-time microarray data. Based on their function, the differentially expressed genes can be grouped into several subcategories, including growth factors and signal transducers, oncogenes and tumor suppressors, tumorspecific antigens, transcriptional factors, transporters, and factors involved in invasion, metastasis, and metabolism. Some genes are novel and unexplored in prostate cancer progression and are of potential interest for follow-up investigation. Reverse transcriptionpolymerase chain reaction (RT-PCR) and real-time RT-PCR were performed to corroborate the microarray results, and 76 differentially expressed genes were validated out of 104 candidates. Expression pattern analyses were performed in these 76 differentially expressed genes, and a series of genes was found to be positively or negatively correlated to prostate cancer progression in the LNCaP prostate cancer progression model and to possess predominant prostate cell specificity. ELF5/ESE-2b and long-chain acyl coenzyme A dehydrogenase (ACADL) expressions were found to be positively associated with malignant progression in LNCaP, C4-2, and C4-2B, and predominantly expressed in prostate cancer cells. Functional evaluation revealed that ELF5/ESE-2b and ACADL expressions contributed to the malignant phenotypes of prostate cancer cells. Accordingly, our microarray data may provide clues for finding novel genes involved in prostate cancer progression to androgen independent and metastasis, and shed light on finding new targets for diagnosis and therapy of prostate cancer.

In vitroandin vivoeffects of a recombinant anti-PSMA immunotoxin in combination with docetaxel against prostate cancer

“…We have chosen these cell lines because they are accepted models representing the androgen-dependent and androgen-independent phenotype of prostate cancer cells [30, 31]. C4-2 cells reflect the CRPC stage in the clinic, which is treated with DOC as a second line therapeutic according to the actual clinical guidelines.…”

Selenium- or Vitamin E–Related Gene Variants, Interaction with Supplementation, and Risk of High-Grade Prostate Cancer in SELECT

“…However, rs7855 is in the 3’ UTR of SOD2 and could be influencing splicing or acting as an enhancer. Also, rs10836233 in CAT is in LD (r 2 = 0.93) with rs11032717 in ELF5 , which is an ETS transcription factor gene that has been implicated in androgen sensitivity and aggressiveness of prostate cancer cell lines (56-58); and rs533425 in CAT is in moderate linkage disequilibrium (R 2 =0.42) with the functional 262 C/T SNP (rs1001179) that has been associated with advanced stage prostate cancer risk. (59)…”

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

“…Enhanced expression of EGFR/ErbB1 had been proven to correlate with high grades of prostate cancer malignancies and contribute to the progression from localized and AD prostate cancer to more metastatic and AI state (34,35), and the phosphorylation level of AKT which was the downstream gene of EGFR had been proven to correlate with androgen receptor level and promote castration-resistant cell growth (25). Importantly, AR was observed to be slightly downregulated in C4-2 (36). Taken together, all these studies indicated EGFR might play a more important role in the process from AD to AI than AR.…”