Lanier H. Ayscue

Role of Estrogen Receptor in the Regulation of Ecto-5′-Nucleotidase and Adenosine in Breast Cancer

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 α 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 ERα 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 ERα 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.

Follicular Lymphoma With a Burkitt Translocation—Predictor of an Aggressive Clinical Course: A Case Report and Review of the Literature

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.

Flow cytometric correlation of the c-myc oncoprotein and cell cycle kinetics of HL60 leukaemia during induced maturation with cytosine arabinoside and dimethylsulphoxide

Abstract The c‐myc oncogene codes for a DNA binding protein that functions in a cell cycle‐related manner. A useful model for studying the relationship of c‐myc expression with cell cycle kinetics is the HL60 cell line. HL60 cells constitutively express high levels of c‐myc mRNA; however, the level can be down‐regulated as the cells are induced to differentiate. We have developed a flow cytometric assay for correlating c‐myc oncoprotein levels with DNA content. C‐myc oncoprotein levels were additionally correlated with c‐myc mRNA levels as determined by slot blot hybridization. Dimethylsulphoxide (DMSO) and cytosine arabinoside were used to induce granulocytic and monocytic maturation respectively. Treatment of HL60 cells with DMSO leads to an increase in the per cent of cells in G1/G0 and a decrease in mean c‐myc mRNA and oncoprotein levels. The cells with G1 DNA content show the greatest decrease in c‐myc protein. ARA‐c treatment of HL60 cells leads to a slowing and an accumulation of cells in S phase with a moderate decrease in mean mRNA and only a slight decrease in mean c‐myc protein levels. These data support the hypothesis that c‐myc is involved in the switch from G1 to G0.