Structural characterization of three novel rat OKL38 transcripts, their tissue distributions, and their regulation by human chorionic gonadotropin.
We previously identified a novel pregnancy-induced growth inhibitory gene, OKL38. To develop a rat model for further characterization of OKL38's role in the initiation and progression of breast and ovarian cancer, we now report the cloning and characterization of three novel rat OKL38 cDNAs that are derived through alternative splicing and differential promoter usage. These three transcripts differ in their 5' untranslated regions but share a common open reading frame that encoded for a 52-kDa protein. OKL38 is mapped to chromosome 19, spanning a region of approximately 15 kb, and contains eight exons. Differential expression of these three rat OKL38 transcripts was observed in liver, kidney, ovary, mammary gland, and uterus. In situ hybridization localized the rat OKL38 transcripts to the luminal epithelial cells of the rat mammary gland and to the granulosa cells in the rat ovary. In vivo studies showed that the RtOKL38-2.0 transcript and protein were regulated by human chorionic gonadotropin in the rat mammary gland and ovary. Importantly, overexpression of RtOKL38-enhanced green fluorescence protein fusion protein in Buffalo rat liver cells resulted in growth inhibition and cell death. Our present findings suggest that OKL38 may function as an effector for human chorionic gonadotropin protection against mammary carcinogenesis, and the availability of the three rat OKL38 cDNAs may help to elucidate the possible role of OKL38 in cellular growth, differentiation, and carcinogenesis.
Ong
Choon Kiat
CK
Laboratory of Molecular Endocrinology, Division of Cellular and Molecular Research, National Cancer Centre of Singapore, 11 Hospital Drive, Singapore 169610.
Ng
Chuan Young
CY
Leong
Caine
C
Ng
Chee Pang
CP
Ong
Chye Sun
CS
Nguyen
Thi Thanh Tuyen
TT
Huynh
Hung
H
D000818:Animals; D001483:Base Sequence; D016923:Cell Death / Q000502:physiology; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005784:Gene Amplification; D014644:Genetic Variation; D016678:Genome; D008099:Liver / Q000378:metabolism / Q000502:physiology; D008969:Molecular Sequence Data; D011247:Pregnancy; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats / Q000378:metabolism*; D011915:Rats, Inbred BUF; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014018:Tissue Distribution
D006063:Chorionic Gonadotropin; D018076:DNA, Complementary; C492609:Osgin1 protein, rat; D011506:Proteins; D012333:RNA, Messenger