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Extracellular Matrix and Androgen Receptor Expression Associated with Spontaneous Transformation of Rat Prostate Fibroblasts¹

Urology Research Laboratory, Department of Urology [M. R. F., Y. S., P. D. G., L. W. K. C.], and Department of Biochemistry and Molecular Biology [D. D. C.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Spontaneous transformation in continuous culture of the androgensensitive rat prostate fibroblast cell line, NbF-1, resulted in an aggressively tumorigenic nonmetastatic phenotype that coincided with few gross chromosome abnormalities. This study identified transformation-associated alterations in extracellular matrix and androgen receptor expression in the NbF-1 cell line. Substantial levels of procollagens I, III, and IV and fibronectin mRNAs were detected in nontumorigenic NbF-1 cells. Laminin B1 and B2 mRNAs were also detectable, but at lower levels. Expression of all six extracellular matrix mRNAs was nonuniformly lower in tumorigenic NbF-1 cells. This decrease in expression was greatest for 2 procollagen IV mRNA, which was reduced 17-fold. Proteoglycans and glycosaminoglycans synthesized by the NbF-1 cultures were also characterized. The NbF-1 cell line expressed chondroitin sulfate proteoglycans predominantly, and expression was reduced 5- to 10-fold in tumorigenic cultures. In contrast to the extensive alterations in the extracellular matrix, measurement of high-affinity androgen binding and androgen receptor mRNA levels showed substantial expression of androgen receptors in both NbF-1 cultures. Cultures of early and late passage NbF-1 cells demonstrated a mitogenic response to dihydrotestosterone. These data indicate (a) that alterations in expression of extracellular matrix components may represent early markers for tumorigenic transformation in prostatic mesenchymal cells and (b) that these changes can occur without disrupting androgen receptor expression and androgen sensitivity.

¹ This work was supported in part by NIH Grant DK-38649 awarded to L. W. K. C. and by the New Development Fund, The University of Texas M. D. Anderson Cancer Center, Houston, TX. M. R. F. was a postdoctoral fellow in the training program in Mammalian Reproduction, University of Texas Health Science Center, and of the NIH during the course of this work.

² Present address: Enders Pediatric Laboratories, 1181, The Children's Hospital, 300 Longwood Ave., Boston, MA 02115.

³ To whom requests for reprints should be addressed, at The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.

Received 6/14/90. Accepted 1/24/91.

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