Interleukin-1alpha protein secretion in breast cancer is associated with poor differentiation and estrogen receptor alpha negativity.
While interleukins (IL)-1alpha and beta are thought to play an important role in malignant disease, little is still known about their expression in breast cancer. We have used reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC) to analyze the expression of IL-1alpha and beta in breast cancer tissues, and compared their expression to estrogen receptor (ER) status and grading. In breast cancer cell lines, we found an inverse correlation between IL-1alpha and beta gene expression and differentiation, and only one highly invasive tumor cell line expressed IL-1alpha protein, while IL-beta was not detectable. Breast cancer tissue expressed variable amounts of IL-1alpha and beta messenger RNA, but consistently high levels of IL-1 type I receptor. IL-1alpha protein was detectable in malignant epithelium and adjacent stroma in 88% of cases. IL-1alpha expression was correlated with poor differentiation (P= 0.002; r= 0.469) and decreasing ERalpha expression (P= 0.004; r=-0.387). Stromal IL-1alpha was confined to areas with low or absent ERalpha protein expression in adjacent tumor epithelium (P= 0.001; r=-0.457). Taken together, we have demonstrated a functional IL-1 system in breast cancer and observed an inverse correlation between IL-1alpha and sex steroid receptor expression. We suggest that the expression of IL-1alpha in poorly differentiated, ERalpha-negative tumors contributes to their malignant phenotype.
Singer
C F
CF
Division of Special Gynecology and Ludwig-Boltzmann-Institute of Clinical Experimental Oncology, University of Vienna Medical Center, Vienna, Austria. Christian.Singer@meduniwien.ac.at
Hudelist
G
G
Gschwantler-Kaulich
D
D
Fink-Retter
A
A
Mueller
R
R
Walter
I
I
Czerwenka
K
K
Kubista
E
E
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D053573:Receptors, Interleukin-1 Type I