ABSTRACT
Human breast cancer cell line Bcap-37 was stably transfected with the plasmid expressing antisense PKC alpha RNA, and cells, in which PKC alpha was inhibited due to antisense PKC alpha RNA, were isolated. Changes in serum-dependent growth in cell culture, cell clonogenicity in soft agar and growth in nude mice were tested, and the expressions of cyclin E and CDK2 were analyzed. After PKC alpha was inhibited, the cells showed that serum-dependent growth and anchorage-dependent growth enhanced, tumorigenicity in nude mice decreased. The results suggest that less aggressive breast cancer phenotypes may be induced by inhibition of PKC alpha. Levels of cyclin E and CDK2 mRNA in cells with antisense PKC alpha RNA were lower than those in control cell. These indicate that signal transduction system with PKC alpha is closely related to cell cycle control system with cyclin/CDK in the functions.
Subject(s)
Breast Neoplasms/metabolism , CDC2-CDC28 Kinases , Cyclin E/biosynthesis , Cyclin-Dependent Kinases/biosynthesis , Protein Kinase C/biosynthesis , Protein Kinase C/genetics , Protein Serine-Threonine Kinases/biosynthesis , Animals , Breast Neoplasms/pathology , Cyclin-Dependent Kinase 2 , Female , Humans , Mammary Neoplasms, Experimental/pathology , Mice , Mice, Inbred BALB C , Mice, Nude , Protein Kinase C-alpha , Signal Transduction , Transfection , Tumor Cells, CulturedABSTRACT
OBJECTIVE: To report a case of agranulocytosis secondary to spironolactone in a patient with cryptogenic liver disease. CASE SUMMARY: A 58-year-old Hispanic woman with cryptogenic cirrhosis was admitted to University Hospital on October 31, 1995. Laboratory data revealed a leukocyte count of 1.0 x 10(3)/mm3 and an absolute neutrophil count (ANC) of 10 cells/mm3. Prior to treatment with spironolactone, the leukocyte count was 10.2 x 10(3)/mm3 and ANC 8400 cells/mm3. Agranulocytosis resolved 5 days following the discontinuation of spironolactone. Results from the bone marrow biopsies before and after treatment with spironolactone suggested that agranulocytosis was caused by the drug's toxic effect on the bone marrow. DISCUSSION: Drug-induced agranulocytosis is a serious adverse effect, occurring at a rate of approximately 6.2 cases per million persons each year. In addition to the case reported here, three other reports of agranulocytosis secondary to spironolactone have been published in the literature. Several factors have been identified that may increase a patient's risk for developing agranulocytosis, including increased age, hepatic or renal impairment, drug dosage and duration, and concurrent medications. CONCLUSIONS: Agranulocytosis secondary to spironolactone is a serious potential adverse effect. Patients with risk factors for developing this adverse effect should be closely monitored since early detection and discontinuation of spironolactone can improve prognosis.
