As in many other cancers, the prognosis of Staurosporine 62996-74-1 breast cancer seems to be intimately related to its cytogenetic disorders. The retinoblastoma tumor suppressor protein regulates G1/Sphase cell cycle progression and is a critical mediator of antiproliferative signaling. RB1 has been reported to be aberrant in approximately 20% of breast cancer cases, and to be associated with a poor disease outcome. However, the regulatory mechanism of RB1 has not been fully clarified yet, although its function has been shown to be regulated mainly by phosphorylation. RB1 status has only infrequently been applied to breast cancer prognostication. RB1-inducible coiled-coil 1 was identified as an RB1 pathway regulator that in particular enhances RB1 transcription. A genetic rearrangement of RB1CC1 has also been suggested to be involved in the tumorigenesis of breast cancer. In addition, RB1CC1 has been reported to be involved in proliferation, growth, apoptosis and autophagy. Recently, we have demonstrated that nuclear RB1CC1 binds to the 201bp upstream GC-rich region of the RB1 promoter and activates RB1 expression. The coordinated expressions of RB1, p16 and p21 influence the proliferation activity in clinical breast cancer. Therefore, the immunohistochemical status of RB1, p53 and RB1CC1 may predict tumor progression and the clinical prognosis of breast cancer patients. Our present study is designed to establish a convenient routine clinical method to evaluate the influence of abnormalities in this newly established pathway i.e. the RB1CC1, p53- RB1 pathway on the long-term prognosis of breast cancer. Nuclear expression of RB1CC1 could be important for tumor suppression. As reported previously, RB1CC1 is located not only inthe nuclei but also in the cytoplasm. Cytoplasmic RB1CC1 has been suggested as a possible equivalent of yeast Atg17, and several studies have indicated that RB1CC1 functions as an essential molecule in autophagy regulation. Autophagy has been implicated in tumorigenesis, but its precise role is ambiguous. It is conceivable that autophagy has different roles in the different stages, or contexts, of tumorigenesis. Young, et al. have reported that autophagy mediates the mitotic senescence, an early window into tumor development. We suggest that cytoplasmic-nuclear transition of RB1CC1 plays a key role in the autophagy-senescence association. Cytoplasmic RB1CC1 seems to play no role as a direct tumor suppressor. In fact, Martin, et al. have reported that PIASy interacts with RB1CC1 and recruits an interacting complex between PIASy and RB1CC1 from cytoplasm into nuclei. In nuclei, PIASy positively activates the p53-p21 signaling pathway together with nuclear RB1CC1. Our recent data demonstrated that nuclear RB1CC1 forms a large transcriptional complex with hSNF5, p53 and/or PIASy that activates a global transcription of genes involved in the RB1 pathway indicating a possible linkage to mitotic senescence and suppresses tumor cell growth.