ALCAM/CD166 protects breast cancer cells against apoptosis and autophagy

• Published in: Medical science monitor Vol. 12; no. 8; pp. BR263 - BR273
• Main Authors: Jezierska, Agnieszka, Matysiak, Wojciech, Motyl, Tomasz
• Format: Journal Article
• Language: English
• Published: United States 01.08.2006
• Subjects: Activated-Leukocyte Cell Adhesion Molecule - genetics; Activated-Leukocyte Cell Adhesion Molecule - metabolism; Antineoplastic Agents - pharmacology; Apoptosis; Autophagy; Biomarkers, Tumor; Breast Neoplasms - pathology; Cell Proliferation - drug effects; Cell Survival - drug effects; Estradiol - pharmacology; Female; Gene Expression; Gene Expression Regulation, Neoplastic - drug effects; Gene Silencing; Genes, bcl-2 - genetics; Humans; Matrix Metalloproteinase 2 - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tamoxifen - pharmacology; Tumor Cells, Cultured
• ISSN: 1234-1010

Activated leukocyte cell adhesion molecule (ALCAM/CD166) is a 105-kDa transmembrane glycoprotein linked with cell migration and development and with cancer progression (malignant melanoma, prostate cancer and, very recently, breast cancer). This report is the first evaluation of ALCAM/CD166 in an estrogen-dependent (MCF-7) and a metastatic (MDA-MB-231) breast cancer cell line and a reference breast cell line (HBL-100). The effects of estrogen and anti-estrogen treatment, bcl-2 overexpression, and ALCAM gene silencing on ALCAM/CD166 protein concentration and cell survival were investigated. Laser scanning cytometry, confocal microscopy, and Western blotting were used for the determination of ALCAM/CD166 protein and biochemical markers of apoptosis and autophagy. 17-beta-estradiol increased and tamoxifen inhibited ALCAM/CD166 expression and survival of MCF-7 cells. Overexpression of the bcl2 gene in MCF-7 bcl2/neo, MDA-MB-231 bcl2/neo, and HBL-100 bcl2/neo cells significantly increased ALCAM/CD166 expression and was accompanied by decreasing MMP-2 concentrations. Appearance of the ALCAM/CD166 protein was noted in HBL-100 bcl2/neo in contrast to an almost undetectable level in HBL-100 cells. ALCAM gene silencing in MCF-7 cells decreased the concentration of BCL-2 and increased levels of apoptosis (89-kDa PARP, active caspase7) and autophagy (MAP1LC3, Beclin1) markers. The above results indicate that ALCAM-ALCAM interactions are crucial to the survival and primary site maintenance of breast cancer cells. Impaired expression of ALCAM/CD166 is associated with the induction of two types of programmed cell death, apoptosis and autophagy, in breast cancer cells. This adhesion molecule can therefore be regarded as a potential novel breast cancer indicator and therapeutic target.