Expression of the Antiapoptotic Proteins Clusterin and Bcl-2 in Laryngeal Squamous Cell Carcinomas

Abstract

Bcl-2 and clusterin genes have been related to the inhibition of apoptosis, an event that plays a key role in malignant transformation and in invasive disease. In this work, we determine the significance of clusterin and bcl-2 expression in a large series of laryngeal carcinomas. We used immunohistochemical methods and in situ hybridization to examine the expression of these proteins. Nontumoral epithelial laryngeal tissues did not express clusterin and bcl-2 proteins. However, 9% (14 out of 154) and 25% of these tumors (39 of 154) had positive clusterin and bcl-2 staining, respectively. Clusterin expression was significantly related to the degree of local invasion and higher bcl-2 expression was found in these clusterin-positive tumors (p < 0.05). Bcl-2 expression was significantly correlated with supraglottic localization, nodal metastases, invasion in depth, and poorly differentiated tumors. However, by multivariate analysis, bcl-2 was shown to be an independent predictor of good prognosis in these tumors (OR = 0.12, 95% CI = 0.02–0.91). These findings indicate that clusterin and bcl-2 are upregulated in laryngeal carcinomas and their expression is related to the invasiveness of these tumors.

Key regulators in bee venom-induced apoptosis are Bcl-2 and caspase-3 in human leukemic U937 cells through downregulation of ERK and Akt

“…Recently, many reports have indicated that ectopic expression of Bcl-2 attenuates anticancer agents to illicit an apoptotic response through a caspase cascade [30,31]. Our data showed that BV treatment results in a progressive expansion of apoptotic population at 48 h and decreased expression of the Bcl-2 protein.…”

Clusterin silencing inhibits proliferation and reduces invasion in human laryngeal squamous carcinoma cells

“…sCLU overexpression reaches a maximum at three to four days post-castration and coincides with the onset of massive cell death [3]. The sCLU level also rises in various malignant tumors, including gastric cancer [4], ovarian cancer [5], breast cancer [6], bladder cancer [7], colorectal cancer [8], hepatocellular carcinoma [9], prostate cancer [10] and laryngeal squamous cell carcinomas [11]. In these cancers, sCLU overexpression has been reported to be closely associated with cancer development and progression.…”

“…Previous study found sCLU was overexpressed in laryngeal carcinomas, and clusterin expression was significantly related to the degree of local invasion [11]. However, whether sCLU may be a target for the treatment of laryngeal carcinomas has not been elucidated.…”

Clusterin Expression in Non-neoplastic Adenohypophyses and Pituitary Adenomas: Cytoplasmic Clusterin Localization in Adenohypophysis is Related to Aging

“…Therefore, to verify this association, further studies in larger series of pituitary adenomas are required. Increased clusterin levels were reported in various neoplasms such as colonic adenomas and carcinomas, hepatocellular carcinomas, ovarian carcinomas, urothelial carcinomas, and laryngeal carcinomas as well [12,13,16,18,23]. However, clusterin localization in pituitary adenomas was not reported previously.…”

“…Upregulation of clusterin was found correlated with aggressive behavior and decreased survival in some neoplasms [12,13,16,18,19,23]. Several authors have proposed that the anti-apoptotic activity of clusterin may account in part for the genesis and biologically aggressive behavior of some types of tumor cells [17,18]. Clusterin has been involved in apoptosis as a proapoptotic or antiapoptotic molecule in a variety of models and under distinct experimental conditions [21].…”