JDP1 (DNAJC12/Hsp40) expression in breast cancer and its association with estrogen receptor status

Abstract

The members of the DnaJ/Hsp40 proteins are highly conserved through evolution, expressed in several tissues and act as co-chaperone regulating protein folding, transport, translational initiation and gene expression. Recently, using cDNA microarray we identified differences in the expression of the JDP1 (DNAJC12) gene, a member of the DnaJ/Hsp40 family, between ER-positive and ER-negative breast tumours. In this study, using quantitative real-time PCR (qPCR) we evaluated the expression pattern of the JDP1 gene in a series of 72 primary breast tumours and investigated the effects of 17ß-estradiol on the expression of the JDP1 in MCF-7 breast cancer cells. Three patterns of JDP1 mRNA expression were identified in the primary breast tumours analysed: normal expression was found in 14% of the cases, under-expression in 50%, and over-expression in 36% of the cases. High levels of JDP1 mRNA expression were significantly associated with estrogen receptor-positive status (p=0.02). No relationship was found between JDP1 mRNA expression and any other clinicopathological characteristics of the patients. Sequence analysis of the promoter region of the JDP1 gene revealed the presence of potential estrogen response elements (EREs), suggesting it to be under the control of estrogen action. We also assessed the effects of 17ß-estradiol (10 nM) on JDP1 mRNA expression in MCF-7 breast cancer cells. The JDP1 transcripts were found to be up-regulated in a time-dependent fashion in MCF-7 cells exposed to 17ß-estradiol treatment. Here we show for the first time that JDP1 is a estrogen target gene and that its expression might be used as a marker of the ER transactivation activity and may have a predictive value for response to hormonal therapy.

Histone acetylation-independent transcription stimulation by a histone chaperone

“…Currently, we have not reached a consensus on the mechanism of gene down-regulation in TAF-I KD cells. However, it is noted that among the genes up-regulated by TAF-I KD, TPD52L1 , TFAP2C , DNAJC12 and TFF1 genes are reported to be estrogen-responsive (1,41–43). The transcription of these genes was increased by estrogen in the estrogen receptor (ER)-positive breast cancer cells, such as MCF-7 cells.…”

Transcriptional up-regulation of PHLDA1 by 17β-estradiol in MCF-7 breast cancer cells

“…Next we examined the effects of 17ß-estradiol and ICI 182,780 on PHLDA1 mRNA expression in MCF-7 cells, a hormoneresponsive breast cancer cell line. The MCF-7 cell line was acquired from the American Type Culture Collection (USA) and cultured as described previously (15). For the experiments, the cells were maintained in RPMI-1640 modified medium, without phenol red, and supplemented with 5% fetal bovine serum or 5% stripped fetal bovine serum, free of steroids, for 48 h before the treatments.…”

The co-chaperone DNAJC12 binds to Hsc70 and is upregulated by endoplasmic reticulum stress

“…While the specific function of DNAJC12 is unknown, the available data indicate that its abundance is regulated by physiological stimuli. De Bessa et al (2006) previously reported that female sex steroids (estrogens) upregulate DNAJC12 mRNA levels in estrogen-sensitive MCF7 human breast cancer cells. In addition, we recently made the interesting observation that DNAJC12 mRNA is upregulated by the transcription factor androgen-induced bZIP/CREB3L4 (AIbZIP) in human prostate cells ).…”