PLU‐1 nuclear protein, which is upregulated in breast cancer, shows restricted expression in normal human adult tissues: A new cancer/testis antigen?

Abstract

The PLU-1 gene is expressed at the level of message in breast cancers and breast cancer cell lines and shows restricted expression in normal adult tissues with the exception of testis. The predicted protein sequence contains several domains, including the PLU domain, which is shared by other proteins involved in transcription and/or development. We have developed a polyclonal antiserum to a C-terminal fragment of the PLU-1 protein, which shows little homology to other family members. Immunohistochemic analysis with the antiserum ␣-PLU-1C confirmed the nuclear localisation of PLU-1. ␣-PLU-1C also reacted with the mouse homologue of PLU-1 (mPlu-1) but not with the closest family member, RBP2. Using Western blot analysis, PLU-1 was shown to be well expressed in breast cancers and breast cancer cell lines, while it was not detected in a range of normal adult tissues. Our results suggest that the PLU-1 protein may belong to the class of testis/cancer antigens. © 2002 Wiley-Liss, Inc. Key words: breast cancer: PLU-1 protein; testis/cancer antigenThe PLU-1 gene was identified as being downregulated in a human mammary epithelial cell line (MTSV1-7) transfected with HER2/c-erbB2, 1 after treatment with the 4D5/HERCEPTIN antibody, which inhibits c-erbB2 signaling. 2 However, in situ hybridisation and Northern blot analyses showed that PLU-1 mRNA is expressed in most breast cancers and breast cancer cell lines, regardless of the level of c-erbB2. 3 However, Northern blot analysis of total mRNA from normal human adult tissues showed high levels of expression in testis and detectable levels in placenta, but levels were undetectable in the other tissues examined.Following our own report on the identification and characterisation of PLU-1, other investigators reported on the cloning of cDNAs of splice and transcriptional variants of the PLU-1 gene. These were referred to as RBP2-H1 4 and RBBP2H1A, 5 respectively. The nomenclature of the splice and transcriptional variants of PLU-1 reflects the high homology between the predicted protein sequence of PLU-1 and the RBP2 6 in conserved domains, particularly in the novel PLU domain. 3,7 PLU-1 binds to a conserved consensus sequence in 2 transcriptions factors through the novel PLU domain. 8 Additionally, PLU-1 was a potent transcriptional repressor and may be involved in gene regulation in breast cancer. We also defined the sequence of mPlu-1 cDNA, which shows at the amino acid level an overall homology with human PLU-1 of 94% and almost 100% identity within the conserved domains. 9 The very conserved sequence of PLU-1 from human to mouse in combination with an almost identical expression pattern in adult tissues and breast cancers in both species suggests a conserved function in breast cancer.The later studies by Vogt et al. 4 and Kashuba et al. 5 on the RNA variants of PLU-1 examined mRNA expression using polyAϩ RNA and probes that would pick up all 3 transcripts. Expression was reported to be less restricted in normal tissues than we observed using total RNA. However, as we repo...

Retinoblastoma-binding protein 2-homolog 1: a retinoblastoma-binding protein downregulated in malignant melanomas

“…The observed deficiency seems to be quite specific for neuroectodermal derived cancers (melanomas and glioblastomas) since RBP2-H1 seems to be abundantly expressed in epithelial cancers. In accordance with our RT-PCR measurements, Barrett et al 7 reported an upregulation of PLU-1 in breast cancer. PLU-1 and RBBP2H1a represent splicing variants of RBP2-H1.…”

“…7,8 More detailed data on the expression of most RBPs in normal and neoplastic tissues are still lacking. While some RBPs, that is, PLU-1 and RBP-1, seem to play a role in breast cancer, 9,10 a possible impact of many other RBPs including RBP2-H1 on human cancer progression has not been investigated, yet.…”

BORIS, a paralogue of the transcription factor, CTCF, is aberrantly expressed in breast tumours

“…MAGE-A was seen frequently in primary ductal breast carcinomas, but not in lobular carcinomas (Otte et al, 2001). Almost 81% of the ductal carcinomas have been shown to express PLU-1 (Barrett et al, 2002).…”

T cells reactive with HLA‐A*0201 peptides from the histone demethylase JARID1B are found in the circulation of breast cancer patients

“…[7][8][9][10] The expression of JARID1B RNA is highest in ER þ ductal carcinomas (www.oncomine.org/), being less well expressed in lobular carcinomas 8 (see Fig. 1).…”

“…[7][8][9][10][11] More recently, expression of this gene in other cancers (bladder, lung, AML) has been reported and the restricted expression in normal tissues confirmed 12 suggesting a specific involvement of PLU-1/JAR-ID1B in malignancy. Moreover, the restricted expression in adult tissues makes the protein a potential therapeutic target, particularly in women.…”