Tamoxifen treatment for breast cancer enforces a distinct gene-expression profile on the human endometrium: an exploratory study.
Tamoxifen treatment for breast cancer increases proliferation of the endometrium, resulting in an enhanced prevalence of endometrial pathologies, including endometrial cancer. An exploratory study was performed to begin to understand the molecular mechanism of tamoxifen action in the endometrium. Gene-expression profiles were generated of endometrial samples of tamoxifen users and compared with matched controls. The pathological classification of samples from both groups included atrophic/inactive endometrium and endometrial polyps. Unsupervised clustering revealed that samples of tamoxifen users were, irrespective of pathological classification, fairly similar and consequently form a subgroup distinct from the matched controls. Using SAM analysis (a statistical method to select genes differentially expressed between groups), 256 differentially expressed genes were selected between the tamoxifen and control groups. Upon comparing these genes with oestrogen-regulated genes, identified under similar circumstances, 95% of the differentially expressed genes turned out to be tamoxifen-specific. Finally, construction of a gene-expression network of the differentially expressed genes revealed that 69 genes centred around five well-known genes: TP53, RELA, MYC, epidermal growth factor receptor and beta-catenin. This could indicate that these well-known genes, and the pathways in which they function, are important for tamoxifen-controlled proliferation of the endometrium.
Gielen
S C J P
SC
Department of Obstetrics and Gynecology, Erasmuc MC University Medical Center Rotterdam, The Netherlands.
Kühne
L C M
LC
Ewing
P C
PC
Blok
L J
LJ
Burger
C W
CW
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm; D016259:Genes, myc / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*; D051996:Transcription Factor RelA / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
D018931:Antineoplastic Agents, Hormonal; C498143:RELA protein, human; D051996:Transcription Factor RelA; D051176:beta Catenin; D013629:Tamoxifen; D066246:ErbB Receptors