Immortalized ovarian surface epithelial cells acquire tumorigenicity by Acrogranin gene overexpression.
Malignant transformation is caused by multi-step genetic mutations, and growth factors are believed to play important roles in developing and maintaining malignant phenotype. However, there is no direct evidence that a specific growth factor contributes to malignant transformation of phenotypically normal cells. In order to assess the function of Acrogranin (also known as granulin epithelial precursor; GEP) in ovarian carcinogenesis, ovarian surface epithelial (OSE) cells, which are supposed to be the origin of primary ovarian epithelial cancer, were transfected with combined genes of hTERT, SV40 LT, and Acrogranin. Introduction of hTERT and SV40 LT was sufficient for immortalizing OSE cells but not enough for tumor formation in nude mice. In contrast, transfection and overexpression of Acrogranin in immortalized OSE cells showed augmented clonogenicity in soft agar and obvious tumorigenicity in nude mice. This is the first study showing evidence that a specific growth factor plays a direct role in malignant transformation in ovarian cancer development.
Miyanishi
Masanori
M
Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Mandai
Masaki
M
Matsumura
Noriomi
N
Yamaguchi
Ken
K
Hamanishi
Junzo
J
Higuchi
Toshihiro
T
Takakura
Kenji
K
Fujii
Shingo
S
D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D000077155:Granulins; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism*; D000077153:Progranulins; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D000077155:Granulins; C120204:Grn protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D012333:RNA, Messenger