BTG2 belongs to a family of structurally related proteins that appear to have antiproliferative properties. BTG2 is
involved in the regulation of the G1/S transition of the cell cycle.
Melamed J, et al 2002 reported the expression of B-cell translocation gene 2 protein in normal
human tissues.
The anti proliferative B-cell translocation gene 2 (BTG2(TIS21/PC3)) is
emerging as an important regulator of cell cycle dynamics. BTG2(TIS21/PC3)
expression increases in response to the induction of DNA damage, cell
differentiation, cell quiescence, cell contact, and as part of a positive
feedback mechanism in response to growth stimulation. The objective of the
present study was to provide further insight into the biological function of
BTG2(TIS21/PC3) by determining the expression levels and cellular localization
of BTG2(TIS21/PC3) in a spectrum of normal human tissues and to determine the
proliferative indices (based on Ki-67 staining) and apoptotic indices (based
on TUNEL assay) in those cell populations where BTG2(TIS21/PC3) was
differentially expressed. Highest levels of BTG2(TIS21/PC3) expression were
seen in kidney proximal tubules, lung alveolar bronchial epithelium and in the
basal cell layer of prostate acini. BTG2(TIS21/PC3) was expressed at
significantly different levels within the different epithelia[ populations of
the kidney (proximal vs distal tubules) and prostate (acinar basal cells vs
lumenal cells). Moderate levels of expression were seen in the acinar cells of
breast and pancreas and in the mucosal epithelium of the intestine. Low levels
of expression were seen in neurons, hepatocyctes, the zona granulosa of the
ovary, round spermatids and thyroid follicles.
NCBI Summary:
The protein encoded by this gene is a member of the BTG/Tob family. This family has structurally related proteins that appear to have antiproliferative properties. This encoded protein is involved in the regulation of the G1/S transition of the cell cycle.
General function
Cell death/survival, Cell proliferation
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Comment
Expression regulated by
FSH, LH
Comment
The B Cell Translocation Gene (BTG) Family in the Rat Ovary: Hormonal Induction, Regulation, and Impact on Cell Cycle Kinetics. Li F et al. The B Cell Translocation Gene (BTG) family regulates gene transcription, cellular differentiation, and inhibits proliferation. The present study investigated the spatiotemporal expression pattern of BTG members and their potential role in the rat ovary during the periovulatory period. Immature female rats (22-23 days old) were injected with PMSG to stimulate follicular development. Ovaries or granulosa cells were collected at various times after hCG administration (n=3/time point). Real-time PCR analysis revealed that mRNA for Btg1, Btg2, and Btg3 were highly induced both in intact ovaries and granulosa cells by 4 to 8 h after hCG treatment although their temporal expression patterns differed. In situ hybridization analysis demonstrated that Btg1 mRNA expression was highly induced in theca cells at 4 h after hCG, primarily localized to granulosa cells at 8 h, and decreased at 24 h. Btg2 and Btg3 mRNA was also induced in granulosa cells, however, Btg2 mRNA was observed in newly forming corpora lutea. Inhibition of progesterone action and the EGF pathway did not change Btg1 and Btg2 mRNA expression, whereas inhibition of prostaglandin synthesis or RUNX activity diminished Btg2 mRNA levels. Overexpression of BTG1 or BTG2 arrested granulosa cells at the G0/G1 phase of the cell cycle and decreased cell apoptosis. In summary, hCG induced Btg1, Btg2 and Btg3 mRNA expression predominately in the granulosa cell compartment. Our findings suggest that the induction of the BTG family may be important for theca and granulosa cell differentiation into luteal cells by arresting cell cycle progression.
Ovarian localization
Granulosa, Luteal cells
Comment
B-cell Translocation Gene 2: Expression in the Rat Ovary and Potential Association with Adenine Nucleotide Translocase 2 in Mitochondria. Park JI et al. The B-cell translocation gene 2 (Btg2) is an anti-proliferative tumor suppressor gene that behaves as a transcriptional regulator. The present study investigated gonadotropin induction of Btg2 in the rat ovary and the mechanism of Btg2 action as a partner of mitochondrial protein adenine nucleotide translocase 2 (Ant2). Transient induction of Btg2 as well as Btg1 mRNA levels by LH/hCG was observed in ovarian granulosa cells. Btg2 protein levels were also stimulated by LH/hCG. LH-induced gene expression of Btg2 required ERK signal pathway. Studies of deletion mutants in HeLa cells showed that deletion of Btg2 C-terminus (Btg2/?C) abolished the interaction with Ant2. In fact, the expression levels of Btg2/?C construct were decreased in mitochondrial fraction. Btg2 was also expressed in mitochondria and interacted with Ant2 in preovulatory granulosa cells. Interestingly, a Btg2/?C construct inhibited an action of Btg2 wild-type on ATP and H(2)O(2) production. These findings demonstrate the gonadotropin stimulation of Btg2 in the ovary and, the physical interaction of Btg2 with Ant2 in mitochondria.