PAR, a novel androgen regulated gene, ubiquitously expressed in normal and malignant cells.

Platica, O; Chen, S; Ivan, Elena; Lopingco, M. C.; Holland, James F.; Platica, Micsunica

doi:10.3892/ijo.16.5.1055

Cited by 10 publications

(29 citation statements)

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“…We previously reported the identification by substraction of a gene designated PAR (prostate androgen regulated) (7) from LNCaP-OM cells, an androgen resistant prostatic carcinoma subline (8). The JTB, jumping translocation gene, with a similar nucleotide sequence was reported by Hatakeyama et al (9).…”

Section: Introductionmentioning

confidence: 99%

PAR, a protein involved in the cell cycle, is functionally related to chromosomal passenger proteins

Platica

Ionescu²,

Ivan³

et al. 2011

Int J Oncol

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Abstract. Prostate androgen regulated (PAR) protein is a 148 amino acid polypeptide ubiquitously expressed in normal cells and overexpressed in many malignancies. Manipulation of PAR mRNA in DU145 and NIH3T3 cells indicated that its expression level is an important determinant of cell in vitro proliferation, clonogenicity in soft agar and in vivo tumorigenicity. In this study, we showed that PAR is a short-lived protein with a peak in G2/M phase. Using immunofluorescent antibodies we showed that PAR moves from centrosomes in prophase and metaphase to spindle midzone in anaphase, and concentrates to midbody in telophase and cytokinesis. During mitosis a fraction of PAR can also be detected in the cytoplasm. PAR pattern of expression and its dynamic localization suggested a functional relationship to chromosomal passenger proteins (CPP). This protein colocalized with Aurora A at centrosomes in metaphase, and with survivin at midbody in telophase and cytokinesis. It also formed complexes with Aurora A, and with survivin, Aurora B and INCENP. In addition, PAR increased Aurora B kinase activity on histone H3. The decreased PAR levels in DU145 cells resulted in defects in centrosome segregation, in failed cytokinesis and chromosome alignment, and in increased number of apoptotic cells, polyploidy and aberrant mitosis. It is known that such defects could lead to genomic instability and tumorigenesis. In this study we also confirm our earlier findings that PAR is overexpressed in many tumors. Due to its involvement in cell cycle and its overexpression in several human cancers PAR could represent an attractive target for therapeutic intervention. IntroductionCellular division is a process which requires a temporal and spatial well-coordinated machinery. Defects in this mechanism can lead to genomic instability, which in turn could result in cell death or cancer (1-3). During the past few years considerable progress has been made towards the understanding the structure and function of the factors involved in cell division. Many mitotic regulators, like chromosomal passenger proteins (4-6) have been identified, but their involvement in mitosis is not yet fully understood. Knowledge of the structure and function of these proteins will allow the control of cell cycle regulatory machinery.We previously reported the identification by substraction of a gene designated PAR (prostate androgen regulated) (7) from LNCaP-OM cells, an androgen resistant prostatic carcinoma subline (8). The JTB, jumping translocation gene, with a similar nucleotide sequence was reported by Hatakeyama et al (9). The 3 kb PAR gene encodes 5 exons and is located on chromosome 1q23 in the epidermal differentiation complex. The PAR cDNA has 1038 bp and encodes a polypeptide of 146 amino acids with an estimated MW of 16 kDa (accession no. AF115850).PAR is ubiquitously expressed in normal tissues and is overexpressed in many malignancies. Manipulation of PAR mRNA in DU145 human androgen resistant prostate cancer cells and NIH3T3 mouse embryonic fibroblast ce...

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Section: Introductionmentioning

confidence: 99%

PAR, a protein involved in the cell cycle, is functionally related to chromosomal passenger proteins

Platica

Ionescu²,

Ivan³

et al. 2011

Int J Oncol

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“…The computer program OLIGO primer analysis software, Version 5.1 (NBI͞Genovus, Plymouth, MN), was used for selecting the appropriate sequencing primers. The 5Ј and 3Ј extremities of TDF cDNA were determined with SMART RACE cDNA amplification kit (BD Biosciences Clontech) and human pituitary poly(A) ϩ RNA, as described (11). The TDF cDNA clone was analyzed with MACD-NASIS PRO sequence analysis software, Version 3.6 (Hitachi, San Bruno, CA) and the BLAST program, seeking homology with other known sequences from GenBank database.…”

Section: Expression Of Transcripts In Xenopusmentioning

confidence: 99%

“…After prehybridization, the blot was hybridized to TDF radioactive probe as described (11). The probe was the DNA fragment between nucleotides 455 and 665 of TDF cDNA clone, amplified by PCR and labeled with [ 32 P]dCTP by random primer technique (11). The normalization was done with a 28S rRNA probe.…”

Section: Expression Of Transcripts In Xenopusmentioning

confidence: 99%

“…The blot was prepared by electrophoresis in a 1.2% denaturing formaldehyde gel and then transferred to nylon membrane of 2 g of poly(A) ϩ RNA obtained from eight normal human tissues (heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas). After prehybridization, the blot was hybridized to TDF radioactive probe as described (11). The probe was the DNA fragment between nucleotides 455 and 665 of TDF cDNA clone, amplified by PCR and labeled with [ 32 P]dCTP by random primer technique (11).…”

Section: Expression Of Transcripts In Xenopusmentioning

confidence: 99%

“…Poly(A) ϩ RNA was prepared from GH3 rat pituitary tumor cell line by using PolyATract mRNA Isolation System III kit (Promega). Northern blot analysis was done as described (11,12).…”

Section: Expression Of Transcripts In Xenopusmentioning

confidence: 99%

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A pituitary gene encodes a protein that produces differentiation of breast and prostate cancer cells

Platica

Ivan

Holland

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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A cDNA clone of 1.1 kb encoding a 108-aa polypeptide was isolated from a human pituitary cDNA library by expression cloning. This protein was named tumor differentiation factor (TDF). The recombinant TDF protein and a 20-aa peptide, P1, selected from the ORF of the gene, induced morphological and biochemical changes consistent with differentiation of human breast and prostate cancer cells. Fibroblast, kidney, hepatoma, and leukemic lymphocytic cell lines were unaffected. Breast and prostate cancer cells aggregated in spheroidlike structures within 24 h of exposure to TDF. This effect was abrogated by a specific affinity-purified rabbit polyclonal anti-P1 Ab. E-cadherin expression was increased in a dose-dependent manner by TDF. Treatment of MCF7 cells with TDF led to production of a lactalbumin-related protein. Peptide P1 significantly decreased the growth of androgen-independent DU145 prostate cancer in severe combined immunodeficient mice. The presence of TDF protein in human sera was detected by the anti-P1 Ab, suggesting a role of TDF in endocrine metabolism. The fact that all activities of TDF can be mimicked by a peptide derived from the encoding TDF sequence opens the possibility of therapeutic applications.M alignant transformation is characterized by the uncoupling of proliferation and differentiation leading to continuing multiplication of cells and the impairment of their ability to progress to complete normal differentiation. Restoration of differentiation of malignant cells has long been considered a potential therapy of cancer (1-5).We have previously reported that an alkaline extract of rat mammosomatotropic tumor MtTW10 induced morphological and biochemical changes in rat and human breast cancer cells indicative of differentiation. Within 24 h of the exposure in vitro, the pituitary tumor extract (PTE) led to aggregation of breast cancer cells, polarization of organelles, the formation of cell junctions and basement membrane, synthesis of mRNA for casein and lactalbumin, and overexpression of E-cadherin (6). The PTE was also effective on prostate cancer cells, inducing cellular changes and overexpression of E-cadherin and prostate-specific antigen.Because this activity was not reproduced by any of the known pituitary hormones or other growth factors, studied alone or in combination, we assumed that the PTE contained a factor, which we called tumor differentiation factor (TDF). Our attempts to isolate and purify this factor by using conventional chromatographic procedures were unsuccessful. Now, using expression cloning, we report the isolation of a human cDNA clone encoding a protein responsible for this tumordifferentiating activity. We have sequenced the clone. Computer analysis indicates that it encodes a polypeptide with no significant homology to any other known sequence in the GenBank database. Our results support the proposition that TDF is a previously unrecognized pituitary factor. Materials and MethodsPituitary cDNA Library. A cDNA library prepared from a growth hormone-producing human ...

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RNA interference‐mediated silencing of the PAR gene inhibits the growth of PC3 cells via the induction of G2/M cell cycle arrest and apoptosis

Zhang

et al. 2007

The Journal of Gene Medicine

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PAR, a novel androgen regulated gene, ubiquitously expressed in normal and malignant cells.

Cited by 10 publications

References 0 publications

PAR, a protein involved in the cell cycle, is functionally related to chromosomal passenger proteins

PAR, a protein involved in the cell cycle, is functionally related to chromosomal passenger proteins

A pituitary gene encodes a protein that produces differentiation of breast and prostate cancer cells

RNA interference‐mediated silencing of the PAR gene inhibits the growth of PC3 cells via the induction of G2/M cell cycle arrest and apoptosis

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