Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ductal morphogenesis in the rodent mammary gland is characterized by the rapid penetration of the stromal fat pad by the highly proliferative terminal endbud and subsequent formation of an arborized pattern of ducts. The role of apoptosis in ductal morphogenesis of the murine mammary gland and its potential regulatory mechanisms was investigated in this study. Significant apoptosis was observed in the body cells of the terminal endbud during the early stage of mammary ductal development. Apoptosis occurred predominately in defined zones of the terminal endbud; 14.5% of the cells within three cell layers of the lumen were undergoing apoptosis compared to 7.9% outside this boundary. Interestingly, DNA synthesis in the terminal endbud demonstrated a reciprocal pattern; 21.1% outside three cell layers and 13.8% within. Apoptosis was very low in the highly proliferative cap cell laver and in regions of active proliferation within the terminal endbud. In comparison to other stages of murine mammary gland development, the terminal endbud possesses the highest level of programmed cell death observed to date. These data suggest that apoptosis is an important mechanism in ductal morphogenesis. In p53-deficient mice, the level of apoptosis was reduced, but did not manifest a detectable change in ductal morphology, suggesting that p53-dependent apoptosis is not primarily involved in formation of the duct. Immunohistochemical examination of the expression of the apoptotic checkpoint proteins, Bcl-x, Bax and Bcl-2, demonstrated that they are expressed in the terminal endbud. Bcl-x and Bcl-2 expression is highest in the body cells and lowest in the nonapoptotic cap cells, implying that their expression is associated with increased apoptotic potential. Bax expression was distributed throughout the terminal endbud independent of the observed pattern of apoptosis. A functional role for Bcl-2 family members in regulating endbud apoptosis was demonstrated by the significantly reduced level of apoptosis observed in WAP-Bcl-2 transgenic mice. The pattern of apoptosis and ductal structure of endbuds in these mice was also disrupted. These data demonstrate that p53-independent apoptosis may play a critical role in the early development of the mammary gland.
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PMID:Apoptosis in the terminal endbud of the murine mammary gland: a mechanism of ductal morphogenesis. 901 21

Ductal development in the pubertal mouse mammary gland is characterized by dramatic morphological changes in the epithelium driven by proliferation of cap and body cells in the terminal endbuds. Recent experiments revealed a coincident and abundant apoptosis in the body cells of these structures. The cells undergoing apoptosis are occasionally restricted to defined regions within the terminal endbud. Localization adjacent to the presumptive lumina suggests that this process functions to sculpt the lumina of the subtending duct. Members of the Bcl-2 family of apoptosis regulatory molecules; Bcl-2 and Bcl-x, appear to have some role in regulating apoptosis in the terminal endbud. Other possible signals which could regulate this developmental process and a model are presented.
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PMID:Programmed cell death in the terminal endbud. 1042

To evaluate our experience of the clinical-pathologic features and outcomes of early-stage Invasive Lobular (ILC) versus Invasive Ductal (IDC) carcinoma treated with breast conservation treatment (BCT). 142 ILC and 1,760 IDC patients were treated with BCT at our institution. All patients underwent breast conserving surgery and radiation therapy (median total dose: 64 Gy). Clinical-pathologic and outcome parameters were analyzed to detect differences between the two cohorts. In addition, COX-2, Bcl-2, and p-53 expression was analyzed from our existing tissue micro-array database. Median follow-up was 6.8 years. A higher percentage of ILC patients presented at >40 years of age (94% ILC versus 89% IDC, p = 0.0353) and had more mammographically occult tumors (p < 0.002). There were no significant differences in T stage, nodal status, family history, final margin, ER/PR/HER-2 status or triple negative tumors (all p-values >0.05). From the immuno-histochemical analysis, expression of p53, COX-2, and Bcl-2 did not differ significantly (all p-values >0.05) between the two cohorts. At 10 years, there was no difference in breast relapse (20% versus 13%, p = 0.25), distant relapse (26% versus 20%, p = 0.28), cause-specific survival (72% versus 84%, p = 0.09) and OS (68% versus 78%, p = 0.08). Patients with ILC had higher contralateral breast relapses (26% versus 12%, p = 0.0006). Patients with early-stage ILC have comparable outcomes to IDC when treated with BCT. Because of the higher risk of contralateral breast cancers for ILC patients, careful evaluation of the contralateral breast will be important in the follow-up of these patients. Future investigations of chemo-preventive strategies to decrease contralateral breast cancers are warranted.
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PMID:The Yale University experience of early-stage invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) treated with breast conservation treatment (BCT): analysis of clinical-pathologic features, long-term outcomes, and molecular expression of COX-2, Bcl-2, and p53 as a function of histology. 1999 77