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Identification of High Mobility Group Protein I(Y) as Potential Progression Marker for Prostate Cancer by Differential Hybridization Analysis¹

Urological Research Laboratory, Departments of Urology [M. J. G. B., F. D., J. A. S.] and Biochemistry [W. J. M. v. d. V.], Radboud University Hospital, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands

One of the major problems in the diagnosis of localized prostatic tumors is to predict the aggressiveness of an individual tumor, which is presumably associated with chance to progression. In an attempt to find molecular markers that are specific for aggressive prostatic cancer cells, we compared steady-state mRNA levels of progressionally related prostatic tumors. The Dunning R-3327-H subline, a relatively benign rat prostatic tumor, was compared to the therefrom derived highly aggressive MatLyLu tumor by differential hybridization analysis. The differential screening revealed 26 complementary DNA clones that detected transcripts overexpressed in MatLyLu. Upon further screening on the entire panel of Dunning R-3327 sublines, it appeared that three clones (pBUS1, pBUS19, and pBUS30), detected transcripts specifically expressed in metastatic rat prostatic tumors. The expression pattern of pBUS19 and pBUS30 suggested a relation between these complementary DNAs. Nucleotide sequence analysis, however, could not yet substantiate this. Computer-assisted comparison of the DNA sequences revealed the presence of rat long terminal repeat-like repetitive elements in pBUS19. The differential expression of repetitive elements in progressionally related tumors is interesting, yet similar findings have not been reported in human malignancies. Nucleotide sequence analysis of pBUS1 indicated that this clone is identical or related to high mobility group protein I(Y), a non-histone nuclear protein. From recent studies it appeared that this protein might be implicated in replication and/or transcription processes and is induced in fast proliferating/undifferentiated cells. The overexpression of high mobility group protein I(Y) correlates rather with metastatic ability than with growth rate; hence it may serve as a valuable marker to identify progressionally advanced prostate cancer cells.

¹ These studies were supported by the Dutch Cancer Foundation (NUKC 90-01) and the Royal Dutch Academy of Arts and Sciences.

² Present address: Center for Human Genetics, University of Leuven, Leuven, Belgium.

³ To whom requests for reprints should be addressed.

Received 8/ 2/90. Accepted 10/26/90.

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