HoxD10 gene delivery using adenovirus/adeno-associate hybrid virus inhibits the proliferation and tumorigenicity of GH4 pituitary lactotrope tumor cells.
Prolactinoma is one of the most common types of pituitary adenoma. It has been reported that a variety of growth factors and cytokines regulating cell growth and angiogenesis play an important role in the growth of prolactinoma. HoxD10 has been shown to impair endothelial cell migration, block angiogenesis, and maintain a differentiated phenotype of cells. We investigated whether HoxD10 gene delivery could inhibit the growth of prolactinoma. Rat GH4 lactotrope tumor cells were infected with adenovirus/adeno-associated virus (Ad/AAV) hybrid vectors carrying the mouse HoxD10 gene (Hyb-HoxD10) or the beta-galactosidase gene (Hyb-Gal). Hyb-HoxD10 expression inhibited GH4 cell proliferation in vitro. The expression of FGF-2 and cyclin D2 was inhibited in GH4 cells infected with Hyb-HoxD10. GH4 cells transduced with Hyb-HoxD10 did not form tumors in nude mice. These results indicate that the delivery of HoxD10 could potentially inhibit the growth of PRL-secreting tumors. This approach may be a useful tool for targeted therapy of prolactinoma and other neoplasms.
Cho
Mi Ae
MA
Division of Endocrinology, Pituitary Tumor Clinic, Research Institute of Endocrinology, Yonsei University College of Medicine, Seoul, Korea.
Yashar
Parham
P
Kim
Suk Kyoung
SK
Noh
Taewoong
T
Gillam
Mary P
MP
Lee
Eun Jig
EJ
Jameson
J Larry
JL
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation; D056742:Cyclin D2; D016213:Cyclins / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D010911:Pituitary Neoplasms / Q000628:therapy*; D015175:Prolactinoma / Q000628:therapy*; D051381:Rats; D014157:Transcription Factors / Q000235:genetics*; D001616:beta-Galactosidase / Q000235:genetics
C486197:Ccnd2 protein, rat; D056742:Cyclin D2; D016213:Cyclins; D018398:Homeodomain Proteins; C490944:Hoxd10 protein, mouse; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; D001616:beta-Galactosidase