Prolactin promotes growth of a spontaneous T cell lymphoma: role of tumor and host derived cytokines.
The present study was conducted to investigate the effect of prolactin (PRL) on the progressive growth of a T cell lymphoma. Using a murine model of a transplantable T cell lymphoma, designated as the Dalton's lymphoma (DL) it is shown that in vivo administration of PRL to tumor bearing mice reduces the survival duration of tumor-bearing host due to an augmentation of tumor growth. In vitro studies demonstrated that PRL directly stimulates the proliferation of DL cells in a dose and time dependent manner. PRL-treated DL cells showed an increase in cell size along with a decrease in cells with apoptotic morphology. Evidence also is presented to show the involvement of tumor and macrophage-derived cytokines: IL-1, IL-2, TGF-beta, and M-CSF in PRL-dependent augmentation of tumor growth. Moreover, PRL treatment was found to inhibit Caspase-activated DNase (CAD) expression in DL cells indicating that PRL acts through modulation of caspase dependent pathway of apoptosis. The study is of novel significance as it demonstrates for the first time that PRL can promote growth of a T cell lymphoma involving host and tumor-derived tumor growth promoting cytokines.
Singh
Mahendra Pal
MP
School of Biotechnology, Banaras Hindu University, Varanasi, 221005, India.
Sharma
Himanshu
H
Singh
Sukh Mahendra
SM
D000818:Animals; D001221:Aspartate Carbamoyltransferase / Q000378:metabolism; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D004080:Dihydroorotase / Q000378:metabolism; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000401:mortality / Q000473:pathology*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011388:Prolactin / Q000494:pharmacology*; D015996:Survival Rate; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
C033626:CAD trifunctional enzyme; D007375:Interleukin-1; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D016173:Macrophage Colony-Stimulating Factor; D011388:Prolactin; D001221:Aspartate Carbamoyltransferase; D020169:Caspases; D004080:Dihydroorotase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)