Apoptosis-Associated Gene Expression in the Corpus Luteum of the Rat1

Abstract

The involution of the corpus luteum (CL) at parturition is an example of physiological apoptosis, a complex process involving massive vascular regression while luteal cells undergo apoptosis. In the present study, changes in gene expression associated with physiological apoptosis were examined. Three genes isolated in our laboratory because of their association with apoptotic processes in the ovary, mammary gland, and prostate served as the focus of our investigation: Y81, Gas-1, and the gene IAP encoding integrin-associated protein. Y81 is a novel gene for which three transcripts are apparent. A Y81 cDNA clone representing the longest transcript has been isolated; it shows an open reading frame exhibiting a region of very high homology with members of the frizzled family, the prototypes of which are cell autonomous polarity genes encoding seven-pass transmembrane receptor proteins, for example the receptor for Wingless. Gas-1 is known as a growth-arrest gene that inhibits DNA synthesis when microinjected into cells. Integrin-associated protein is a beta 3-integrin-binding protein for which, recently, a thrombo-spondin-binding activity has been recognized. These three genes, all sharply up-regulated in the course of physiological involution processes in the ovarian CL, in mammary gland, and in prostate, seem promising candidates-by virtue of their specific expression in distinct tissues undergoing programmed cell death-as mediators of stimuli leading to apoptosis and subsequent phagocytosis. In this study, sulfated glycoprotein-2, previously observed in many instances of physiological apoptosis, was further employed as an indicator for incipient apoptosis, and stromelysin was followed as a marker for the tissue remodeling activity that is intimately associated with apoptosis during involution.

Role of DDC-4/sFRP-4, a secreted Frizzled-related protein, at the onset of apoptosis in mammary involution

“…We have previously shown that DDC-4/sFRP-4 was upregulated in various tissues undergoing physiological apoptosis. 3,4,45 The new data show that DDC-4/sFRP-4 expression is a stimulus rather than a consequence of the apoptotic program in the mammary gland. Since DDC-4 is an sFRP and thus thought to sequester Wnt ligands, we propose a role for DDC-4/sFRP-4 in abrogating a Wnt-regulated survival pathway, the latter possibly signaling via PKB/Akt.…”

“…45,53 The rabbit affinity purified anti-DDC-4 serum was used at a dilution of 1:100 on tissue sections after microwave treatment in 50 mM sodium citrate for 5 min at reduced energy (maximum temperature, 901C). For BrdU labeling, females were injected I.P.…”

“…The TUNEL reaction was performed as previously described 45 using either BODIPY-dUTP visualized directly in the fluorescence microscope (Molecular Probes, Eugene, OR, USA) or digoxigenin-11 dUTP detected with anti-digoxigenin Fab antibodies conjugated to alkaline phosphatase (Roche Diagnostics, Rotkreuz, Switzerland). Fixation was exactly as for in situ hybridization.…”

Hypothyroidism prolongs corpus luteum function in the pregnant rat

“…At the end of pregnancy in the rat, the most evident sign of luteal regression is the abrupt decrease in P 4 secretion by the luteal cells, which is followed by their apoptotic death (Guo et al 1998). The factors responsible for initiating and mediating luteal regression are very complex.…”

β-Catenin Stability, Cyclin D1 and Frizzled Proteins Expression in Human Breast Cancer and Their Relation with the Prognosis

“…The ro le of sFRP downre gu la ti on in bre ast can cers has been furt her con fir med by a number of aut hors. [30][31][32][33] In this study, we in ves ti ga ted; 1-Ex pres si on le vels of β-ca te nin, cyclin D1, sFRP1 and sFRP2 in the bre ast can cer tis su e, 2-The inf lu en ce of me no pa u sal sta tus, es tro gen re cep tor, pro ges te rone re cep tor, c-erbB2, p53 po si ti vity, lymph no de in vol ve ment and cli ni cal TNM sta ge on the expres si on of β-ca te nin, cyclin D1, sFRP1 and sFRP2, 3-The ef fect of the eva lu a ted pa ra me ters on β-ca te nin, cli ni copat ho lo gi cal prog nos tic pa rame ters inc lu ding his to lo gi cal gra de, lymph no de in vol ve ment and TNM sta ge.…”