Regulators of Proliferation and Apoptosis in Carcinoma of the Larynx

Abstract

Expression of interrelated gene products regulating cell proliferation and apoptosis may be disordered in squamous cell carcinoma (SCC) of the larynx compared with normal squamous mucosa. Certain of these abnormalities, alone or in combination, may be of prognostic significance in low-stage carcinomas of the larynx. A retrospective study of archival material was made. Expression of the Bcl-2 family of apoptosis-related genes (bcl-2, bcl-X, mcl-1, and bax) and the proliferation- and apoptosis-related genes p53 and cyclin D-1 were determined in 40 low-T-stage laryngeal carcinomas and in uvular epithelium from patients without SCC. Among the antiapoptotic members of the Bcl-2 family, Bcl-X and Mcl-1 showed more intense and widespread staining than Bcl-2 itself in both normal squamous mucosa and SCC. The well-ordered expression patterns of Bcl-2-related proteins found in normal epithelium were lost in SCC, and patterns of expression varied widely among individual tumors. Also, mean expression levels for Bax and cyclin D-1 were significantly lower than in normal epithelium (P = .036 and P = .009, respectively), whereas expression of p53 was higher in tumors (P = .034). Expression of Bcl-X and Mcl-1 was greater in poorly differentiated than in well-differentiated tumors (P = .014 and P = .031, respectively). No associations were seen between marker expression patterns and clinical outcome in this group of patients. Bcl-x and Mcl-1 appear to be the most abundantly expressed antiapoptotic proteins of the Bcl-2 family in both normal squamous mucosa and SCC of the larynx. Multiple genes regulating proliferation and apoptosis are expressed abnormally in laryngeal SCC compared with normal epithelium. In particular, loss or measurable decrease in expression of the proapoptotic protein Bax in tumors may contribute to the deranged growth control of SCC. Further study is needed to evaluate the prognostic significance of particular patterns of disordered expression of proteins regulating proliferation and apoptosis in SCC of different head and neck sites.

Cyclin D1 Protein Tissue Detection in Laryngeal Cancer

“…In the examined specimens, accumulation of p53 protein and elevated CCND1 expression levels correlated with each other, in contrast to a previous immunohistochemical study [9] . p53 overexpression, though attributable to a missense mutation in some squamous cell carcinomas [9] , is not an exact correlate of mutation, because chain-termination mutations prevent protein synthesis and some tumors overexpress p53 in the absence of apparent mutations.…”

“…Overexpression of CCND1 leads to abnormal cellular proliferation which underlies processes of tumorigenesis; CCND1 can thus function as a cooperative oncogene in cell transformation [6] . The CCND1 gene is abnormal or abnormally expressed in many human cancers [9] . The CCND1 gene (also known as PRAD1) is localized on chromosome 11q13 and encodes a 295-aa protein [8] .…”

Genotyping of Patients with Sporadic and Radiation-Associated Meningiomas

“…Both genes have a role in the cell cycle control pathway regulating the transition through G 1 -S phase (22). Activation and overexpression of the cyclin D1 gene have been found in a variety of malignant tumors (breast, head and neck, esophagus, larynx, and lung) but also in a subset of benign parathyroid adenomas (55)(56)(57)(58)(59)(60)(61). Noteworthy, the G-A sequence variant (G870A) in exon 4 of cyclin D1 creates an alternative splice site, encoding a protein with an altered COOH-terminal domain (62).…”

Arsenic trioxide enhances the cytotoxic effect of cisplatin in head and neck squamous cell carcinoma cell lines

“…Mcl-1 is a member of the Bcl-2 family and is involved in inhibiting cell death in various cell types. Mcl-1 is highly expressed in HNSCC (17). …”