JDP1 (DNAJC12/Hsp40) expression in breast cancer and its association with estrogen receptor status.
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 17beta-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 17beta-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 17beta-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.
De Bessa
Simone Aparecida
SA
Departamento de Radiologia, Disciplina de Oncologia da Faculdade de Medicina da Universidade de São Paulo, 01246-903, São Paulo, Brazil.
Salaorni
Sibeli
S
Patrão
Diogo F C
DF
Neto
Mário Mourão
MM
Brentani
Maria Mitzi
MM
Nagai
Maria Aparecida
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics*; D013629:Tamoxifen / Q000494:pharmacology
C484558:DNAJC12 protein, human; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D012097:Repressor Proteins; D013629:Tamoxifen; D004958:Estradiol