Summary

Apoptosis, a normal physiological form of cell death, is criticallyinvolved in the regulation of cellular homeostasis. If the delicatebalance between cell death and cell proliferation is alteredby a defect in the normal regulation of apoptosis signaling, a cellpopulation is able to survive and accumulate, thereby favoringthe acquisition of further genetic alterations and promotingtumorigenesis. Dysregulation of programmed cell death mechanismsplays an important role in the pathogenesis and progressionof breast cancer, as well as in the responses of tumors totherapeutic intervention. Overexpression of anti-apoptoticmembers of the Bcl-2 family such as Bcl-2 and Bcl-XL has beenimplicated in cancer chemoresistance, whereas high levels ofpro-apoptotic proteins such as Bax promote apoptosis andsensitize tumor cells to various anticancer therapies. Recently,a new member of the Bcl-2 family, BCL2L12, was cloned. The BCL2L12 gene is constitutively expressed in many tissues, suggestingthat the encoded protein serves an important functionin different cell types. In the present study, the expression ofBCL2L12 gene was analyzed by reverse transcription-PCR(PT-PCR) in 70 breast cancer tissues. Our results indicate thatBCL2L12 positive breast tumors are mainly of lower stage (I/II)or grade (I/II) (p=0.02 or p=0.04 respectively). Cox regressionanalysis revealed that BCL2L12 expression is positively relatedto disease-free (DFS) and overall survival (OS) at both univariateand multivariate analysis (p=0.021, p=0.029, p=0.032,p=0.044 respectively). Kaplan-Meier survival curves also demonstratedthat patients with BCL2L12-positive tumors havesignificantly longer DFS and OS (p=0.002 and p<0.001 respectively).BCL2L12 expression may be regarded as a new independentfavorable prognostic marker for breast cancer.