Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various molecular markers have been used for the detection of circulating breast cancer cells in blood by reverse transcriptase-polymerase chain reaction (RT-PCR). Using nested RT-PCR, we compared the specificity and sensitivity of human mammaglobin (hMAM), epidermal-growth-factor receptor (EGF-R), and cytokeratin 19 (CK-19) expression as markers for circulating carcinoma cells in the peripheral blood of patients with breast cancer. Blood samples from 12 patients with ductal carcinoma in situ, 133 patients with invasive breast cancer, 20 patients with hematological malignancies, 31 healthy volunteers, and tumor tissues from 40 patients with invasive breast cancer were screened for mRNA encoding hMAM, EGF-R, or CK-19 by nested RT-PCR. In all breast cancer tissues, mRNA for hMAM, EGF-R, and CK-19 was detectable. In blood samples from patients with invasive breast cancer, 11 (8%), 13 (10%), and 64 (48%) were positive for mRNA encoding hMAM, EGF-R, or CK-19, respectively. Blood samples from none of the healthy volunteers and patients with hematological disorders were positive for hMAM, while CK-19 mRNA was found in the blood of 12 (39%) healthy volunteers and transcripts for EGF-R and CK-19 were detectable in 5 (25%) and 2 (10%), respectively, of the patients with hematological malignancies. Only hMAM mRNA expression in blood correlated with clinical parameters such as nodal status, metastasis, and CA 15-3 serum levels. In summary, hMAM transcripts detectable in blood by RT-PCR represent the most specific molecular marker for hematogenous spread of breast cancer cells. With the nested RT-PCR method, aberrant EGF-R mRNA expression might occasionally be found in hematological malignancies, whereas CK-19 mRNA expression proved to be rather nonspecific. The prognostic value of hMAM RT-PCR-based tumor cell detection in peripheral blood should be further tested and validated in prospective studies.
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PMID:Mammaglobin gene expression: a superior marker of breast cancer cells in peripheral blood in comparison to epidermal-growth-factor receptor and cytokeratin-19. 1090 52

Sentinel lymph node (SLN) biopsy for breast cancer staging has been widely accepted because it is more sensitive and less morbid than axillary dissection. Sentinel nodes can be thoroughly scrutinized using a variety of techniques increasing the detection of micrometastases; however, the clinical relevance of micrometastases has been challenged. The available data suggest that the prognostic significance of axillary metastases is related to the size of the metastases, and the best data suggest that outcome for patients with metastases < 0.2 mm is similar to patients with node-negative disease. This would argue against the use of ultrasensitive tests such as reverse transcriptase polymerase chain reaction. Immunohistochemistry upstages 2%-20% of hematoxylin and eosin-negative sentinel nodes, and additional nodal metastases are identified in approximately 10% of completion axillary dissections prompted by an immunohistochemistry (IHC)-positive sentinel node. This would appear to be a good reason to perform IHC and act on the results. Because micrometastases can be artifactual, SLN biopsy in ductal carcinoma in situ can lead to harmful overtreatment and is best performed in the context of clinical trials. Lymphoscintigraphy has allowed the detection of alternate drainage patterns to internal mammary, infraclavicular, and supraclavicular lymph nodes. Although patients are occasionally identified who have metastases to these basins but not the axilla, this information will not impact the decision for chemotherapy in most cases. Internal mammary SLN biopsy may have value in patients with tumors < 1 cm, but requires additional evaluation in clinical trials.
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PMID:Cytokeratin staining and other sentinel node controversies. 1275 79

S100 proteins are involved in many biological processes. S100A7 and S100A9 have been shown to be markedly upregulated both in ductal carcinoma in situ of the breast and in psoriasis. We have examined the relationship between keratinocyte differentiation and the expression of the two proteins. Using Western blot analysis and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), both S100A7 and S100A9 were shown to be induced in normal primary keratinocytes (HEKn), when differentiation was promoted by high extracellular calcium, loss of contact with extracellular matrix and confluent conditions, as previously reported for S100A7 in mammary epithelial cells. Differentiation was confirmed by using RT-PCR for the differentiation marker keratin-1. Using immunohistochemistry with monoclonal antibodies, we compared the expression of the two proteins in a spectrum of conditions of dysregulated keratinocyte differentiation. We found a strikingly similar distribution of the proteins. Their expression correlated with the degree of keratinocyte differentiation. They were both absent in undifferentiated basalioma and strongly expressed in carcinoma in situ, as well as in keratoacanthoma and differentiated squamous cell carcinoma. In normal epithelium, they were expressed in the superficial, differentiated region of the epithelium rather than in the basal region. These findings support the hypothesis that these two S100 proteins are involved in keratinocyte differentiation.
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PMID:Expression patterns of S100A7 (psoriasin) and S100A9 (calgranulin-B) in keratinocyte differentiation. 1574 May 87

Hypoxia and acidosis are microenvironmental selection forces during somatic evolution in breast carcinogenesis. The effect of cobalt chloride (CoCl(2))-induced hypoxia on the expression of hypoxia-inducible factor (HIF)-1alpha, glucose transporter 1 (GLUT1), and carbonic anhydrase IX (CAIX) was assessed in breast cancer cells derived from primary sites (HCC1395 and HCC1937) and metastatic sites (MCF-7 and MDA-MB-231) by reverse transcriptase-polymerase chain reaction and immunoblotting. We analyzed these proteins' expression in tissue samples from normal breast tissue, usual ductal hyperplasia (DH), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) using immunohistochemistry. CAIX mRNA was expressed constitutively in MDA-MB-231 cells but not in the other three cell lines. CAIX mRNA expression was increased after CoCl(2)-induced hypoxia in all four breast cancer cell lines. The expression of HIF-1alpha and GLUT1 proteins was increased after CoCl(2)-induced hypoxia in all breast cancer cell lines tested. Hypoxia significantly increased CAIX protein expression in primary cancer cells but not in metastatic ones. HIF-1alpha was not expressed in benign breast tissue, whereas it was significantly expressed in DH, ADH, DCIS, and IDC (p < 0.001). GLUT1 and CAIX were expressed only in DCIS (56.8% and 25.0%) and IDC (44.1% and 30.5%), with higher expression in high grade DCIS than low/intermediate grade DCIS (79.2% vs. 30.0%, p = 0.001 and 37.5% vs. 10.0%, p = 0.036, respectively). High CAIX expression was significantly associated with poor histological grade of IDC (p = 0.005). During breast carcinogenesis, the role of HIF-1alpha changes from response to proliferation to tumor progression. GLUT1 expression (glycolytic phenotype) and CAIX expression (acid-resistant phenotype) may result in a powerful adaptive advantage and represent an aggressive phenotype.
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PMID:Hypoxia and metabolic phenotypes during breast carcinogenesis: expression of HIF-1alpha, GLUT1, and CAIX. 2052 21