High Bak Expression Is Associated with a Favorable Prognosis in Breast Cancer and Sensitizes Breast Cancer Cells to Paclitaxel

Abstract

Breast cancer has become the leading cause of cancer-related death among women. A large number of patients become resistant to drug chemotherapy. Paclitaxel (Taxol) is an effective chemotherapeutic agent used to treat cancer patients. Taxol has been widely used in human malignancies including breast cancer because it can stabilize microtubules resulting in cell death by causing an arrest during the G2/M phase of the cell cycle. Pro-apoptotic Bcl-2 antagonist killer 1 (Bak) plays an important role in Taxol-induced apoptosis in breast cancer. In our present study, we investigated the expression of the Bak protein and clinicopathological correlations in a large sample of breast cancer tissues by immunohistochemistry. We found that the percentage of high scores of Bak expression in breast cancer was significantly lower than that of the non-cancerous breast control tissue. In addition, lower Bak expression was positively associated with the clinical TNM stage of breast cancer with a significant decrease in overall survival compared with those with higher Bak expression especially in the Luminal and HER2 subtypes. Importantly, higher Bak expression predicted a favorable clinical outcome in the cases treated with Taxol indicated by a higher overall survival than that of patients with lower Bak expression especially in Luminal and HER2 subtypes. Furthermore, these results were confirmed in vitro since overexpression of Bak sensitized breast cancer cells to Taxol by inhibiting proliferation and promoting apoptosis; in contrast, downregulation of Bak through siRNA transfection inhibited Taxol induced-apoptosis. Therefore, our results demonstrate that Bak acts as a sensitive biomarker and favorable prognostic factor for Taxol treatment in breast cancer. The restoration of Bak expression would be therapeutically beneficial for Taxol resistant breast cancer patients.

High IKKα expression is associated with reduced time to recurrence and cancer specific survival in oestrogen receptor (ER)‐positive breast cancer

“…This is in keeping with previous reports that demonstrate that both BAK1 and BBC3 are associated with prognosis and or response to therapy in breast cancer. [36][37][38] It therefore appears that IKKa selective inhibitors would be most beneficial to patients with ER-positive tumours and may function via induction of apoptosis and inhibition of proliferation. Studies from the literature demonstrate that IKKa is involved in regulation of oestrogen-dependent genes such as cyclin D1 and c-myc, resulting in increased proliferation.…”

“…are associated with prognosis and or response to therapy in breast cancer [37][38][39] . Figure 3C and also for the cells used in the wst-1 assays Figure 4A.…”

TCF21 functions as a tumor suppressor in colorectal cancer through inactivation of PI3K/AKT signaling

“…The human cancer tissues and matched adjacent normal tissues were used for immunohistochemistry analysis, as described previously 9. Tissues were subjected to citrate-based antigen retrieval using 10 mM sodium citrate buffer (pH 6.0).…”

Annexin A2 is an independent prognostic biomarker for evaluating the malignant progression of laryngeal cancer

“…IHC staining was performed as previously described (13). Briefly, the tissue sections (4 µm thick) were deparaffinized and hydrated and then retrieved using citrate buffer in boiling water for 15 min.…”