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Identification of the human pituitary tumor transforming gene (hPTTG) family: molecular structure, expression, and
L Chen1, R Puri, E J Lefkowitz
1Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Abstract:
In an attempt to determine the mechanism of human tumorigenesis, we have searched for oncogenes and recently reported the molecular cloning of a potent oncogene (hPTTG) from human testis. hPTTG mRNA is expressed at high levels in various human tumors and tumor cell lines. Overexpression of hPTTG in the mouse fibroblast cell line (NIH 3T3) results in an increase in cell proliferation, induces cellular transformation in vitro, and promotes tumor formation in nude mice. The hPTTG gene isolated from the human genomic library consists of five exons and four introns and spans over 10kb. In the studies reported here, we further investigated the possibility of the presence of additional genes homologous to hPTTG in the human genome, which was first indicated by Southern blot analysis of the human genomic DNA and chromosomal mapping of the hPTTG gene using DNA from humanxhamster hybrid cell lines in PCR. Sequencing and restriction map analysis of the additional genomic clones identified two intronless genes homologous to hPTTG. This finding was confirmed by the chromosomal location of the second gene to chromosome 4p15.1 and the third gene to chromosome 8q13.1. Based on the similarity in sequences, we proposed that hPTTG be renamed hPTTG1 and the new genes be named hPTTG2 and hPTTG3. hPPTG2 was found to be 91% identical and hPPTG3 89% identical with hPPTG1 at the amino acid level. Northern blot and reverse transcriptase/polymerase chain reaction (RT/PCR) analyses of the mRNA from various human tissues revealed differential expression of the hPTTG2 and hPTTG3 genes in normal and tumor tissues, suggesting that these genes may be associated with tumorigenesis.
Insights
Researchers identified two new human genes, hPTTG2 and hPTTG3, homologous to the oncogene hPTTG1. These genes show differential expression in normal and tumor tissues, suggesting a role in human tumorigenesis.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- The human pituitary tumor transforming gene (hPTTG) is a known oncogene implicated in tumorigenesis.
- hPTTG overexpression in cell lines and animal models demonstrates its potential to drive cancer progression.
- Previous studies indicated the possibility of additional hPTTG-homologous genes in the human genome.
Purpose of the Study:
- To identify and characterize additional genes homologous to the human oncogene hPTTG.
- To determine the chromosomal locations and sequence similarity of these novel genes.
- To investigate the expression patterns of these genes in normal and cancerous human tissues.
Main Methods:
- Southern blot analysis of human genomic DNA.
- Polymerase chain reaction (PCR) with human-hamster hybrid cell lines for chromosomal mapping.
- Sequencing and restriction map analysis of genomic clones.
- Northern blot and reverse transcriptase/polymerase chain reaction (RT/PCR) for mRNA expression analysis.
Main Results:
- Two novel intronless genes, designated hPTTG2 and hPTTG3, were identified as homologous to hPTTG1.
- hPTTG2 and hPTTG3 were mapped to chromosomes 4p15.1 and 8q13.1, respectively.
- hPTTG2 shares 91% amino acid identity, and hPTTG3 shares 89% amino acid identity with hPTTG1.
- Differential expression of hPTTG2 and hPTTG3 was observed in various normal and tumor tissues.
Conclusions:
- The identification of hPTTG2 and hPTTG3 expands the PTTG gene family in humans.
- The distinct expression profiles of hPTTG2 and hPTTG3 in tumor tissues suggest their potential involvement in human tumorigenesis.
- Further research into the functional roles of hPTTG2 and hPTTG3 is warranted to understand their contribution to cancer development.