Role ofBcl-2, Bax, andBak in spontaneous apoptosis and proliferation in neuroendocrine lung tumors: Immunohistochemical study

Abstract

Fifty-six primary neuroendocrine lung tumors were examined morphologically and histologically and their apoptosis level was determined. Malignant carcinomas were characterized by increased apoptotic index and enhanced expression ofBcl-2, Bak, p53, and Ki-67 compared to typical carcinoid. However, apoptosis in these tumors was not completed. Proteins of the Bcl family play an important role in the regulation of spontaneous apoptosis in neuroendocrine lung tumors. Bcl-2 accumulating in the nucleus is a morphological analogue of phosphorylated inactive form of this protein, which does not inhibit apoptosis. Expression of Bcl-2 and Bax decreases in small-cell lung carcinoma (SCLC) with metastases indicating attenuation of apoptosis and development of metastatic clones resistant to apoptosis induces.

LIGHT sensitizes IFNγ–mediated apoptosis of HT-29 human carcinoma cells through both death receptor and mitochondria pathways

“…Increased expression of Bak might be enough to antagonize the antiapoptotic effect of anti-apoptosis Bcl-X L and upregulated Ser (112)-phosphor-Bad. It has been shown that Bak is the most important pro-apoptosis Bcl-2 family member, whose function is to determine whether or not apoptosis proceeds in the cell [26][27][28][29]. This observation correlates with the observation that Bid expression levels remained unaltered, while phospho-(Ser112)-Bad and Bak were upregulated in MDA-MB-231 breast carcinoma cells treated with LIGHT in the presence of IFNγ [19].…”

Reduction in BCL-2 levels by 26S proteasome inhibition with bortezomib is associated with induction of apoptosis in small cell lung cancer

“…BCL-2 is overexpressed in 69-90% of SCLC tumors as well as in a majority of the currently available cell lines [11][12][13][14]. Furthermore, expression of BCL-2 is higher in metastatic tumors compared to localized disease [15,16]. Most importantly, increased BCL-2 expression confers chemoresistance in SCLC by inhibiting apoptosis [15,[17][18][19].…”

In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability

“…In fact, Bcl-2 overexpression, mainly with nuclear localization, together with a high Bcl-2/Bax ratio, was correlated directly with an elevated spontaneous apoptosis index (31)(32)(33), and with the absence of metastasis in SCLC tumors (34). The relationship between Bcl-2 overexpression and tumor stage is less clear, but an inverse correlation between Bcl-2 levels and cancer progression has already been pointed out (29,(34)(35)(36). In addition, there are cases of reduced Bcl-2 levels upon in vitro acquisition of resistance to cisplatin (37).…”

“…It has been demonstrated that, regardless of the frequently observed Bcl-2 overexpression in SCLC cell lines (2) and tumors (3), there is no correlation between Bcl-2 expression and resistance to therapy and/or patient survival (26)(27)(28)(29)(30). In fact, Bcl-2 overexpression, mainly with nuclear localization, together with a high Bcl-2/Bax ratio, was correlated directly with an elevated spontaneous apoptosis index (31)(32)(33), and with the absence of metastasis in SCLC tumors (34). The relationship between Bcl-2 overexpression and tumor stage is less clear, but an inverse correlation between Bcl-2 levels and cancer progression has already been pointed out (29,(34)(35)(36).…”