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Gene Expression during the Early Phases of Regression of the Androgen-dependent Shionogi Mouse Mammary Carcinoma¹

Department of Cancer Endocrinology, Cancer Control Agency of British Columbia, Vancouver, British Columbia, Canada V5Z 4E6 [P. S. R., N. B., H. C.], and Department of Urology, Columbia University, New York, New York 10001 [R. B., M. B.]

The effects of castration on gene expression were measured in the androgen-dependent Shionogi mouse mammary carcinoma. From 0 to 144 h after castration, polyadenylated RNA from the tumors was analyzed by Northern blotting for the expression of genes associated with cell maintenance (ß-actin and -tubulin), cell growth and differentiation (c-fos and c-myc), and cell stress and death (heat shock 70 and TRPM-2). During the first 48–72 h after castration, the tumor continued to increase its mass but thereafter (72–144 h) began to regress. Throughout, the concentration of polyadenylated RNA recovered and the expression of both ß-actin and -tubulin remained relatively constant, implying that in the surviving cells there are no major decreases in RNA synthesis. By comparison, c-myc exhibited a small increase in relative expression during the entire period examined, whereas c-fos displayed a transient peak at 12 h after castration, suggesting that this gene is acutely sensitive to androgen withdrawal. Heat shock protein 70 displayed a pattern similar to that of c-fos; however, the transient rise in the level of heat shock protein 70 expression could be induced by sham operations alone. The concentration of the transcripts encoding TRPM-2 rose only when tumor regression was most evident (72–144 h after castration). Thus, gene expression in the Shionogi carcinoma following castration can be grouped according to those genes which show little or no response, those which are acutely sensitive, and those which show a late effect and are more closely affiliated with cell death.

¹ This research was supported by grants from the National Cancer Institute of Canada and the Medical Research Council of Canada.

² To whom requests for reprints should be addressed, at Department of Cancer Endocrinology, Cancer Control Agency of British Columbia, 600 West 10th Ave., Vancouver, British Columbia, Canada V5Z 4E6.

Received 3/29/88. Revised 7/18/88. Accepted 8/ 9/88.

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