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(American Journal of Pathology. 1999;154:1335-1343.)
© 1999 American Society for Investigative Pathology

Short Communication

Differentially Expressed Genes in Hormone Refractory Prostate Cancer

Association with Chromosomal Regions Involved with GeneticAberrations

Andrew P. Stubbs*, Paul D. Abel{dagger}, Matthew Golding*, Gurjeet Bhangal*{ddagger}, Qin Wang*{ddagger}, Jonathan Waxman{ddagger}, Gordon W.H. Stamp* and El-Nasir Lalani*

From the Departments of Histopathology,*
Surgery,{dagger}
and Oncology,{ddagger}
Imperial College School of Medicine, Hammersmith Campus, London, United Kingdom

Differential gene expression between the androgen sensitive human prostate cancer cell line LNCaP and an insensitive clonal variant, LNCaP-r, was demonstrated by suppression subtractive hybridization. Twenty-one sequences were identified of which 9 are homologous to known genes, 11 are represented by expressed sequence tags (ESTs), and 1 is novel. We present data for 5 of 7 sequences confirmed to be differentially expressed by Northern blot analysis and semiquantitative RT-PCR. Only one gene, fibronectin (FN), was highly overexpressed (>60-fold) in LNCaP-r cells, consistent with previously reported overexpression of FN in prostate cancer. Four sequences were down-regulated in LNCaP-r cells, including an inactive variant of the E2 ubiquitin conjugating enzyme (UEV-1), a novel metalloproteinase-related collagenase (PM5), and a potential tumor suppressor gene (breast basic conserved gene, BBC1). UEV-1 is multifunctional, regulates the cell cycle via cdk1, has homology to MMS2 and likewise functions as a DNA protection protein, and also has homology to TSG101. Aberrant splice variants of TSG101 occur frequently in both breast and prostate cancer, but its mechanism of action is unknown. FN, BBC1, and UEV-1 localize to regions of chromosomal aberration (2q3.4, 16q24.3, and 20q13.2, respectively) associated with advanced prostate cancer and thus may be highly relevant to disease progression.




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