Antitumor activity of the 16-kDa prolactin fragment in prostate cancer.
The 16-kDa prolactin (PRL), derived from the proteolytic cleavage of wild-type 23-kDa PRL, has been shown to have antiangiogenic activity. Such an antiangiogenic activity may have an effect on tumor growth in vivo. Here we examined the effect of 23-kDa and 16-kDa PRL on tumor growth, and the potential of using recombinant 16-kDa human PRL for prostate cancer therapy. The effects of 23-kDa PRL and 16-kDa PRL on the tumorigenicity of prostate cancer cells in vivo were studied. Using an adenovirus transfer vector to achieve high efficiency 23-kDa and 16-kDa PRL transfection in DU145 and PC-3 human prostate carcinoma cell lines, we demonstrated that expression of 16-kDa PRL in the prostate cancer cells markedly reduced their ability to form tumors in a xenograft animal model. These studies established that the 16-kDa PRL has antitumor activity in vivo, presumably as a result of its antiangiogenic effect. Interestingly, 23-kDa PRL showed a weak and transient suppression of prostate tumor growth. The weak antitumor activity of 23-kDa PRL may be because of the production of 16-kDa PRL from 23-kDa PRL by the tumor cells. Thus, the apparent effect of 23-kDa PRL on the growth of DU145 and PC-3 cells in vivo may result from the combined effects of 23-kDa PRL and 16-kDa PRL. These results suggest that the 16-kDa PRL has potential as a treatment agent in prostate cancer.
Kim
Jeri
J
Departments of Genitourinary Medical Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Luo
Weiping
W
Chen
Dung-Tsa
DT
Earley
Karen
K
Tunstead
James
J
Yu-Lee
Li-Yuan
LY
Lin
Sue-Hwa
SH
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002455:Cell Division / Q000235:genetics; D004730:Endothelium, Vascular / Q000473:pathology; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics*; D011388:Prolactin / Q000096:biosynthesis / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014162:Transfection; D019076:Transgenes; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D010446:Peptide Fragments; D011388:Prolactin