RESUMEN
PURPOSE: The purpose is to understand the expression of ecto-5'-nucleotidase (eN), an adenosine producing enzyme with potential roles in angiogenesis, growth, and immunosuppression, in estrogen receptor (ER)-negative and -positive breast cancer. EXPERIMENTAL DESIGN: We investigated the regulation of eN expression at the mRNA and protein levels by alpha in a panel of breast cancer cell lines that differ in ER status and invasive and metastatic potential. We also determined rates of adenosine formation in cells with high and low eN expression and in ER+ cells treated with estradiol. RESULTS: ER-negative cells express high eN protein and mRNA levels and produce up to 104-fold more adenosine from AMP and ATP. Estradiol and antiestrogen treatments confirm that eN mRNA and protein expression and adenosine generation are negatively regulated through the ER. Endogenous expression of eN in ER- cells transfected with ERalpha and phorbol ester-induced eN expression in ER+ cells was strongly suppressed by estradiol, suggesting a dominant function of ER. Finally, an examination of 18 clinical breast cancer samples that were analyzed for both ER status and eN expression by Martin et al. (Cancer Res., 60: 2232-2238, 2000) revealed a significant inverse correlation between ER and eN status. CONCLUSIONS: Our results show for the first time that eN is negatively regulated by ERalpha in dominant fashion and suggests that eN expression and its generation of adenosine may relate to breast cancer progression. Additionally, increased expression of eN in a subset of ER-negative cells may serve as a novel marker for a subset of more aggressive breast carcinoma.
Asunto(s)
5'-Nucleotidasa/metabolismo , Adenosina/metabolismo , Regulación Neoplásica de la Expresión Génica , Receptores de Estrógenos/metabolismo , Adenosina/química , Adenosina Desaminasa/metabolismo , Adenosina Monofosfato/metabolismo , Adenosina Trifosfato/metabolismo , Northern Blotting , Western Blotting , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Progresión de la Enfermedad , Estradiol/metabolismo , Estrógenos/metabolismo , Genes Dominantes , Humanos , Invasividad Neoplásica , Metástasis de la Neoplasia , Ésteres del Forbol/metabolismo , Plásmidos/metabolismo , ARN Mensajero/metabolismo , Factores de Tiempo , TransfecciónRESUMEN
Follicular lymphoma is an indolent lymphoma characterized by the (14;18) translocation, which leads to aberrant expression of Bcl-2. Translocations involving 8q24 are most commonly associated with Burkitt lymphoma and result in c-Myc overexpression. We report a case of follicular lymphoma of predominant small cleaved-cell type (grade 1) associated with both a t(14;18)(q32;q21) and a t(8;22)(q24;q11). The 8q24 translocation predicted an aggressive clinical course, as the lymphoma transformed into acute lymphoblastic leukemia within a year of initial diagnosis. Routine cytogenetic analysis is recommended at initial diagnosis of follicular lymphoma to better identify abnormalities that may predict prognosis and influence therapy.
