Consistently, a significant direct correlation between HMGA1 and Bcl-2 overexpression has been observed in human breast carcinomas harboring wild-type p53.
Expression of Bcl-2 is associated with resistance to hormone therapy and recurrence in prostate carcinomas, whereas in lung and breast carcinomas it is associated with a better prognosis.
Angiopoietin-2, an angiogenic regulator, promotes initial growth and survival of breast cancer metastases to the lung through the integrin-linked kinase (ILK)-AKT-B cell lymphoma 2 (Bcl-2) pathway.
The present data indicate that androgens can down-regulate bcl-2 protooncogene levels via an androgen receptor-mediated mechanism, thus providing a novel mechanism for their known inhibitory effect on breast cancer cell growth.
Tea phytoconstituents are known to modulate myriad molecular events which include prominent regulators of intracellular signaling, such as phosphatidylinositide 3-kinase/protein kinase B/nuclear factor-κB, epidermal growth factor receptor, vascular endothelial growth factor, B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein in the development and progression of breast carcinoma.
More recently, Bcl-2 has been recognized as an important prognostic factor in breast cancer, although controversies persist with respect to the significance of its expression.
The results indicated that MVs have a size range of 500-1500 nm, and the viability of MCF-7 was significantly decreased when treated by different concentrations of MVs and it was confirmed when apoptosis-related genes' expression level was measured by real-time reverse transcription polymerase chain reaction whereas demonstrated that apoptosis genes including Bax, P53, P21, and EP300 (2<sup>- ΔΔ CT</sup>) and ΔCT values were expressed significantly in MCF-7 treated by MVs higher than those nontreated, and decrease of Bcl-2 expression level in MVs-treated MCF-7 was also significant as an antiapoptosis-related gene.
Borrelidin has limited anti-cancer effects in bcl-2 overexpressing breast cancer and leukemia cells and reveals toxicity in non-malignant breast epithelial cells.
We have earlier reported that Ubc9 promotes tumor growth in the xenograft mouse model using breast cancer cell line MCF-7 in part through regulation of Bcl-2 expression.
There was significant co-expression of TFF3 with AKT1 (p = 0.0365), BCl2 (p = 0.0152), and NF Kappa-B (p = 0.0243) in breast carcinoma cases with residual carcinoma following neoadjuvant therapy which support the role of TFF3 in chemoresistance.
Breast cancer in women aged less than 35 years also had higher histologic grade and higher frequency of bcl-2-negative tumor than that found in the 36- to 50-year age group.
The reduction of Bak may play important roles in malignant development of breast cancer to acquire estrogen independency, counteracting the reduced Bcl-2.
In this context, we have previously demonstrated that under hypoxia bcl-2 promotes hypoxia-inducible factor-1 (HIF-1)-mediated vascular endothelial growth factor (VEGF) expression in melanoma and breast carcinoma.
TP53 mutations, histological grade, and expression of bcl-2 (but not LOH or c-erbB-2 expression) all predicted for relapse-free as well as breast cancer-specific survival in univariate analysis (Ps between <0.0001 and 0.0155), but only tumor grade was found to be predictive in multivariate analysis (P = 0.01 and P = 0.0007, respectively).
Because anti-apoptotic BCL-2 family proteins can affect the threshold for induction of apoptosis and thus limit the effectiveness of the chemotherapeutic payload, we examined whether inhibition of BCL-2/X<sub>L</sub> would enhance the efficacy of T-DM1 in five HER2-expressing patient-derived breast cancer xenograft models.
The study results indicate that Bcl-2 and S-phase analysis of fine-needle samples of breast carcinomas provide a convenient tool for the assessment of these tumors.