Table 3.
S100 Proteins in Cancer and Normal Tissues
| Name | Chrom. | RAGE binding | p53 binding | Normal tissue expression | Expression in cancer | Cancer notes |
| S100A1 | 1q21 | Possibly, (antagonizes S100A4-RAGE interactions) | Yes – TET and NRD | Highest in heart, also expressed in kidney, liver, skin, brain, lung, stomach, testis, muscle, small intestine, thymus and spleen | Renal carcinoma | |
| S100A2 | 1q21 | Not observed | Yes – TET and NRD | Kerotinocytes, breast epithelial tissue, smooth muscle cells and liver | Thyroid, prostate, lung, oral, and breast carcinomas; melanoma | Mostly down-regulated but upregulated in some cancer types |
| S100A3 | 1q21 | Not observed | Differentiating cuticular cells in the hair follicile | |||
| S100A4 | 1q21 | Yes, coexpressed with RAGE in lung and breast cancer | Chondrocytes, astrocytes, Schwann cells, and other neuronal cells | Thyroid, breast and colorectal carcinomas; melanoma; bladder and lung cancers | Overexpression is associated with metastases and poor prognosis | |
| S100A5 | 1q21 | Not observed | Limited areas of the brain | Astrocytic tumors | Overexpressed | |
| S100A6 | 1q21 | Yes, coexpressed with RAGE in lung and breast cancer | Yes – TET | Neurons of restricted regions of the brain | Breast cancer, colorectal carcinoma | Not found in healthy breast or colorectal |
| S100A7/A7A | 1q21 | Yes, Zinc dependant activation | Kerotinocytes, dermal smooth muscle cells | Breast carcinoma, bladder and skin cancers | Not expressed in non-cancer tissues except for skin | |
| S100A8/A9 | 1q21 | Possibly (activates NF-kB in endothelial cells) | Expressed and secreted by neutrophils | Breast and colorectal carcinomas, gastric cancer | Upregulated in premetastatic stage, then downregulated | |
| S100A9 | 1q21 | See S100A8 | See S100A8 | See S100A8 | ||
| S100A10 | 1q21 | Not observed | Several tissues, highest in lung, kidney, and intestine | |||
| S100A11 | 1q21 | Yes – inflammation induced chondrcyte hypertrophy | Yes – TET | Keratinocytes | Colorectal, breast, and renal carcinomas; bladder, prostate, and gastric cancers | Decreased expression is an early event in bladder carcinoma, high expression is associated with better prognosis in bladder and renal cancer patients but worse prognosis in prostate and breast |
| S100A12 | 1q21 | Yes – Inflammatory processes (activates endothelial cells and leukocytes) | Granulocytes, keratinocytes | Expressed in acute, chronic, and allergic inflammation | ||
| S100A13 | 1q21 | Yes – stimulates its own uptake by cells | Broadly expressed in endothelial cells, but not vascular smooth muscle cells | Upregulated in endometrial lesions | ||
| S100A14 | 1q21 | Not observed | Broadly expressed in many tissues, but not detected in brain, skeletal muscle, spleen, peripheral blood leukocytes | Overexpressed in ovary, breast and uterus tumors, Down-regulated in kidney, rectum and colon tumors | ||
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S100A15 (name withdrawn, see S100A7) |
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| S100A16 | 1q21 | Not observed | Broadly expressed with highest levels esophagus, lowest in lung, brain, pancreas and skeletal muscle | Upregulated in lung, pancreas, bladder, thyroid and ovarian tumors | ||
| S100B | 21q22 | Yes – RAGE -dependant, cytochrome C mediated activation of caspase-3 | Yes – TET and NRG | Astrocytes | Melanoma | Overexpressed in melanoma |
| S100G | Xp22 | Not observed | Pancreas, intestine, mineralized tissues | Pancreatic cancer | Overexpressed >100-fold | |
| S100P | 4p16 | Yes – stimulates cell proliferation and survival | Placenta | Prostate and gastric cancers | Overexpressed | |
| S100Z | 5q14 | Not observed | Pancreas, lung, placenta, and spleen | Decreased expression in cancer | ||
p53 binding domains: TET: Tetramerization, NRD: Negative regulatory domain