R. Yu et al., Pituitary tumor transforming gene (PTTG) regulates placental JEG-3 cell division and survival: Evidence from live cell imaging, MOL ENDOCR, 14(8), 2000, pp. 1137-1146
The pituitary transforming gene, PTTG, is abundantly expressed in endocrine
neoplasms. PTTG has recently been recognized as a mammalian securin based
on its biochemical homology to Pds1 p. PTTG expression and intracellular lo
calization were therefore studied during the cell cycle in human placental
JEG-3 cells. PTTG mRNA and protein expressions were low at the G(1)/S borde
r, gradually increased during S phase, and peaked at G(2)/M, but PTTG level
were attenuated as cells entered G(1). In interphase cells, wild-type PTTG
, an epitope-tagged PTTG, and a PTTG-EGFP conjugate all localized to both t
he nucleus and cytoplasm, but in mitotic cells, PTTG was not observed in th
e chromosome region. PTTG-EGFP colocalized with mitotic spindles in early m
itosis and was degraded in anaphase. Intracellular fates of PTTG-EGFP and a
conjugate of EGFP and a mutant inactivated PTTG devoid of an SH3-binding d
omain were observed by real-time visualization of the EGFP conjugates in li
ve cells. The same cells were continuously observed as they progressed from
G(1)/S border to S, G(2)/M, and G(1). Most cells (67%) expressing PTTG-EGF
P died by apoptosis, and few cells (4%) expressing PTTG-EGFP divided, where
as those expressing mutant PTTG-EGFP divided. PTTG-EGFP, as well as the mut
ant PTTG-EGFP, disappeared after cells divided. The results show that PTTG
expression and localization are cell cycle-dependent and demonstrate that P
TTG regulates endocrine tumor cell division and survival.