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Deficiency
of a Novel Retinoblastoma Binding Protein 2-Homolog is a Consistent Feature
of Sporadic Human Melanoma Skin Cancer |
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Thomas Vogt,
Max Kroiss, Michael McClelland, Claus Gruss, Bernd Becker, Anja Katrin Bosserhoff,
Gerhard Rumpler, Thomas Bogenrieder, Michael Landthaler, and Wilhelm Stolz |
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Department
of Dermatology (TV, MK, CG, BB, AKB, GR, TB, ML, WS), University of Regensburg,
Germany; and Sidney Kimmel Cancer Center (MM), La Jolla, California |
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SUMMARY: Using RNA arbitrarily
primed PCR, the authors selected for transcripts with cell cycle-related
differential expression in cultured human melanocytes. Among the partial
cDNAs cloned, a novel cDNA was identified, which showed 54% identity
to the recently cloned cDNA of the retinoblastoma binding protein-2 (RBP2).
The 6.5-kB full-length cDNA of this RBP2-related gene, termed RBP2 homolog
1 (RBP2-H1), was obtained from a human teratocarcinoma cDNA library. Two
independent libraries from human malignant melanomas were negative. A computerized
sequence analysis revealed highly conserved motifs with possible functional
meaning: two domains that, in the RBP2 homolog, mediate the binding and
interaction with the proteins encoded by the retinoblastoma susceptibility
gene, the TATA-binding protein, and the oncoprotein rhombotin 2; in addition,
two DNA-binding zinc finger/leukemia-associated protein motifs were detected.
Because a functional role in cell-cycle control and transcriptional activation
can be envisioned, we investigated the expression of this novel transcript
in normal fetal and adult tissues, as well as tissues of benign and malignant
melanocytic tumors. By conducting multiple Northern blot, RT-PCR, and in
situ hybridization analyses, the authors showed that the corresponding mRNA
is expressed in virtually all normal tissues. Accordingly, they found RBP2-H1
expression in microdissected tissue samples from benign melanocytic nevi
(n = 10). In contrast, the transcript is significantly down-regulated
or even lost in tissue samples from human malignant melanomas (n
= 13), melanoma metastases (n = 10), and melanoma cell lines (n
= 7). The authors concluded that the loss or down-regulation of RBP2-H1
expression could be a useful molecular marker for a transformed phenotype
in the human melanocytic system. |
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