Role of tumor necrosis factor‐α and its receptors in human benign breast lesions and tumors (in situ and infiltrative)

Abstract

The aim of the present study was to characterize the expression pattern of tumor necrosis factor (TNF)-α α α α and its receptors in breast samples (benign diseases, in situ carcinomas and infiltrating carcinomas), and to compare these results with those obtained previously for interleukin-6, p53 and p21 using the same samples in order to elucidate the effects of these cytokines on the proliferationapoptosis equilibrium. Immunoexpression of TNF-α α α α and its receptors (TNFRI and TNFRII) were studied by western blotting and immunohistochemistry. The percentage of samples positive for TNF-α α α α and TNFRII was higher in in situ carcinoma than in benign breast diseases, and TNFRII was even higher in infiltrating tumors. The percentage of samples positive for TNFRI was similar in the three groups. For the three proteins and in the three patient groups, immunoreactions were observed in the peripheral cytoplasm. In the positive samples, immunostaining for TNF-α α α α was more intense in infiltrating tumors than in the other two patient groups, whereas immunostaining for both receptors was higher in in situ carcinoma than in benign breast diseases, and even higher in infiltrating tumors. Comparing the TNF-α α α α results with previous results for mtp53, p21 and interleukin-6, we found an association between the expression of these four proteins and increasing malignancy. TNF-α α α α might be an important factor in breast cancer promotion as its proliferation and survival effects seems to be enhanced through the increased expression of TNFRII. Also, the pro-apoptotic pathway of TNFRI could be inhibited by p21 (which appeared increased in breast cancer), altering TNFRI effects in promoting the expression of several factors, such interleukin-6, which contribute to tumor promotion. (Cancer Sci 2006; 97: 1044-1049) T umor necrosis factor (TNF)-α seems to exert a key role in promoting many tumors to breast cancer. TNF-α is a 17-kDa polypeptide that was first described as a serum-derived substance that causes tumor cell death, (1) and is involved in skin carcinogenesis and the spread of a variety of carcinomas and sarcomas. It can induce tumor necrosis by affecting tumor vascularization and initiating apoptotic cell death, but paradoxically, it also can promote cell proliferation.(2,3) The action of TNF-α is mediated by two distinct receptors, named TNFRI (55 kDa) and TNFRII (75 kDa), both of which show a similar affinity for TNF-α in humans.(4-6) TNFRI is the major mediator of most TNF-α activities, (7) including apoptosis. (8,9) However, cell proliferation through Nuclear Factor kappa B(NF-κB) transcription factor activation (10,11) has also been reported in fibroblasts.(12) TNFRII has been described to mediate proliferation in some cells by acting as a thymocyte. (13) Another cytokine related to TNF-α and cell proliferation is interleukin (IL)-6. Recent studies have reported that high expression of IL-6 is associated with proliferation markers in breast cancer.(14) Both TNF-α and IL-6 could also be related to different f...

Tumor necrosis factor-alpha and its receptors in epithelial ovarian cancer.

“…In the present study, we detected TNF-α and TNF-R1 in more than 84% of cases with benign ovarian lesions, whereas TNF-R2 was detected in a low number of cases (24%). These results are in accordance with García Tunón et al, who reported higher immunoexpression of TNF-α in breast pathologies than in benign breast lesions [21].…”

Increased H2O2 level in exhaled breath condensate in primary breast cancer patients

“…TNF might be an important factor in breast cancer promotion as its proliferation and survival eVects seem to be enhanced through the increased expression of TNF receptor. Recent studies showed that expression of TNF and its receptors not only increased in in situ breast cancer but also increased even further in inWltration stage with TNF expression increasing in parallel with increased malignancy (Garcia-Tunon et al 2006). Also, the pro-apoptotic pathway of TNF receptor could be inhibited by p21, which appeared increased in breast cancer, altering TNF receptor eVects in promoting the expression of several factors, such as interleukin-6, which contribute to tumor promotion (Garcia-Tunon et al 2006).…”

Eryngium foetidum Suppresses Inflammatory Mediators Produced by Macrophages

“…The elevated expression of TNF-α in pre-cancerous and tumor cells was related to the progression of malignant diseases, such as prostate cancer, breast cancer, and cervical carcinoma. (Ahmed et al, 2001;Michalaki et al, 2004;Garcia-Tunon et al, 2006). Serum TNF-α level also correlated with the extent of therapy responses.…”