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Volume 270, Number 12, Issue of March 24, 1995 pp. 6615-6618
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Oral Contraceptive-induced Expression of Prostate-specific Antigen in the Female Breast (*)

(Received for publication, September 26, 1994; and in revised form, November 17, 1994)

He Yu (1) (2) Eleftherios P. Diamandis (1) (2)(§) Maria Monne (3) Carlo M. Croce (3)

From the  (1)Department of Clinical Biochemistry, The Toronto Hospital, Toronto Western Division, Toronto, Ontario M5T 2S8, Canada, the (2)Department of Clinical Biochemistry, University of Toronto, Toronto, Ontario M5G 1L5, Canada, and the (3)Department of Microbiology-Immunology, Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107


ABSTRACT

Prostate-specific antigen (PSA) is widely used as a tumor marker of prostatic adenocarcinoma. We recently found that 30% of breast tumors produce PSA and that PSA is a favorable prognostic marker in female breast cancer. We measured immunoreactive PSA in cytosolic extracts of normal breast tissue from eight women receiving no medication and one woman who was receiving the progestin-containing oral contraceptive Brevicon. None of the eight cytosolic extracts of normal breast tissue contained appreciable amounts of immunoreactive PSA. However, left and right breast tissues from the woman receiving Brevicon contained high levels of PSA. This immunoreactive species was shown to have a molecular weight identical to that of seminal PSA. Furthermore, reverse transcription of RNA and polymerase chain reaction amplification produced a 571-base pair cDNA that hybridized to a labeled cDNA PSA probe. Upon sequencing, the cDNA polymerase chain reaction product was found to have 100% homology with cDNA from prostatic tissue. PSA production by breast carcinoma cell lines was achieved after in vitro stimulation with norethindrone and ethinylestradiol. Our data suggest that PSA can no longer be regarded as a specific prostatic protein because it is produced by breast tumors with good prognosis and by normal breast tissue after steroid hormone stimulation.


FOOTNOTES

*
This work was supported by grants from the Cancer Research Society Inc., Montreal, Canada, the University Research Incentive Fund of the province of Ontario, and the Ontario Section of the Canadian Breast Cancer Foundation (to E. P. D.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked ``advertisement'' in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§
To whom reprint requests should be addressed: Dept. of Pathology and Laboratory of Medicine, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5, Canada. Tel.: 416-586-8443; Fax: 416-586-8628.

(^1)
The abbreviations used are: PSA, prostate-specific antigen; HPLC, high performance liquid chromatography; PCR, polymerase chain reaction; bp, base pair(s); ACT, alpha(1)-antichymotrypsin.

(^2)
H. Yu, M. Giai, E. P. Diamandis, D. J. A. Sutherland, M. A. Levesque, R. Roagna, R. Ponzone, P. Sismondi, and D. Katsaros, submitted for publication.

(^3)
M. Monne and C. M. Croce, manuscript in preparation.


©1995 by The American Society for Biochemistry and Molecular Biology, Inc.


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