Associated effects of bromocriptine on neoplastic progression of mouse mammary preneoplastic hyperplastic alveolar nodule line C4 and on hyperplastic alveolar nodule-infiltrating and splenic lymphocyte function.
Progression of the mouse mammary preneoplastic hyperplastic alveolar nodule (HAN) line C4 to carcinoma can be enhanced by stimulators and depressed by inhibitors of host lymphocyte function (W.Z. Wei et al., Cancer Res., 49: 2709-2715, 1989). The purpose of the present study was to ask whether prolactin (PRL), a regulator of both mammary epithelial and lymphoid cells, might be a factor in the association between lymphocytic function and HAN progression. Daily administration of bromocriptine, a suppressor of pituitary PRL secretion, increased the latency period and decreased the incidence of tumor development in HAN bearing mice. Bromocriptine treatment suppressed in vitro responsiveness of HAN-infiltrating lymphocytes and, to some extent, spleen cells, to T- and B-cell mitogens, without altering the relative proportion of lymphocytic subsets. Suppression could be partially reversed by PRL treatment. Natural killer cell activity of HAN-infiltrating lymphocytes was also reduced by bromocriptine. In vitro incubation with anti-PRL antisera inhibited both lymphocyte mitogen responsiveness and natural killer activity in a concentration-dependent manner. PRL reversed this inhibition also. Altogether, these results demonstrate a correlation among tumor development, PRL levels, and lymphocyte function and suggest that an immune-endocrine network involving PRL may play a role in C4 HAN progression.
Tsai
S J
SJ
Breast Cancer Biology Program, Michigan Cancer Foundation, Detroit 48201.
Loeffler
D A
DA
Heppner
G H
GH
D000818:Animals; D001971:Bromocriptine / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D006965:Hyperplasia / Q000473:pathology; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects*; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011230:Precancerous Conditions / Q000097:blood / Q000276:immunology / Q000473:pathology*; D011388:Prolactin / Q000097:blood*
D001971:Bromocriptine; D011388:Prolactin