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Influence of Pituitary Grafts or Prolactin Administrations on the Hormone Sensitivity of Ovarian Hormone-independent Mouse Mammary MXT Tumors¹

Laboratoire d'Histologie, Faculté de Médecine, Université Libre de Bruxelles, 2 rue Evers [R. K., Y. d. L., A. D., J-L. P.], and Clinique de Dépistage de l'Institut J. Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles, 1 rue Héger-Bordet [R. P.], B-1000, Brussels, Belgium

The sensitivity of MXT mouse mammary tumors to ovarian hormones was assessed by the following parameters: growth in vivo; presence or absence of estrogen receptors and progesterone receptors; and histological differentiation. A spontaneous evolution from hormone sensitivity (HS) to hormone independence (HI) was observed when the tumors underwent monthly transplantation onto intact recipient mice, with the tumors fulfilling the criteria of HI tumors after the 12th transplantation. In contrast, the tumors recovered most of the criteria of hormone sensitivity when pituitary isografts were placed under the kidney capsules of HI tumor-bearing animals or when these animals received daily administrations of prolactin over several months. Sensitivity to 17ß-estradiol, progesterone, or prolactin was further assessed by actinomycin binding on the nucleus and thymidine labeling index, both measured by autoradiography. These technical approaches revealed that 17ß-estradiol and prolactin stimulated the thymidine labeling index of both HI (despite the lack of detectable estrogen receptors) and HS MXT tumors whereas progesterone influenced only that of HS cancers. The three hormones significantly stimulated [³H]actinomycin D binding within HS tumors but not within HI ones. However, such "HI" tumors were characterized by increased actinomycin binding and thymidine labeling index in comparison with HS neoplasms. Thus, all the data presently reported strongly suggest that prolactin is able to restore the hormone-sensitive phenotype within so-called MXT hormone-independent tumors.

¹ This work was supported by grants awarded by the Institut pour l'encouragement de la Recherche Scientifique dans l'Industrie et l'Agriculture (IRSIA), by the Fonds de la Recherche Scientifique Médicale (FRSM), and by the Fonds Cancérologique de la Caisse Générale d'Epargne et de Retraite" (CGER), Belgium.

² To whom requests for reprints should be addressed.

³ Grantees of Institut pour l'encouragement de la Recherche Scientifique dans l'Industrie et l'Agriculture (IRSIA, Belgium).

Received 1/ 4/88. Revised 9/27/88. Accepted 3/ 6/89.

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