Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biologic properties of breast cancer in men that might reflect alterations in pathogenesis from the disease in women were examined. We studied 22 tumors from males, 18 invasive carcinomas, three of which were papillary, and three in situ tumors of which one was papillary, and one papilloma. Our data support the previously reported high incidence of papillary carcinoma in men. Estrogen receptor status and the expression of cancer-associated antigens recognized by antibodies DF3, B73.2, SP-1, and c-erbB-2 were compared to matched tumors from females. Immunocytochemistry was performed on formalin-fixed, paraffin-embedded sections using standard avidin-biotin techniques; anti-PSA was used to exclude the possibility of metatastic prostate cancer, and 12 cases of gynecomastia were included as nonmalignant controls. The incidence of estrogen receptor positivity was higher in tumors from males (73%) than from females (54%), as has been reported previously. The range of expression of all breast cancer antigens tested in male tumors was similar to that observed in females, but some interesting differences were noted. With the exception of the anti-mucin DF3, all the antibodies reacted only with neoplastic tissues. Expression of the oncoprotein c-erbB-2 was lower (17%) in males than in females (33%), despite the preponderance in men of the large-cell type carcinomas that have been associated with c-erbB-2 expression. Unexpectedly, the pregnancy-associated hormone detected by SP-1 was expressed in 33% of tumors from males and, in contrast to females, was found in less differentiated tumors.
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PMID:Immunocytochemical characterization of male breast cancer. 136 97

Transforming growth factor-alpha (TGF-alpha) is thought to be the major autocrine factor controlling growth in epidermal cells. To explore further the role of TGF-alpha in epidermal growth and differentiation, we used a human keratin K14 promoter to target expression of rat TGF-alpha cDNA to the stratified squamous epithelia of transgenic mice. Unexpectedly, the only regions of epidermis especially responsive to TGF-alpha overexpression were those that were normally thick and where hair follicle density was typically low. This included most, if not all, body skin from 2-day- to 2-week-old mice, and ear, footpad, tail, and scrotum skin in adult mice. In these regions, excess TGF-alpha resulted in thicker epidermis and more stunted hair growth. Epidermal thickening was attributed both to cell hypertrophy and to a proportional increase in the number of basal, spinous, granular, and stratum corneum cells. During both postnatal development and epidermal differentiation, responsiveness to elevated TGF-alpha seemed to correlate with existing epidermal growth factor (EGF) receptor levels, and we saw no evidence for TGF-alpha-mediated control of EGF receptor (EGFR) expression. In adults, no squamous cell carcinomas were detected, but benign papillomas were common, developing primarily in regions of mechanical irritation or wounding. In addition, adult transgenic skin that was still both sensitive to TGF-alpha and subject to mild irritation displayed localized regions of leukocytic infiltration and granular layer loss, characteristics frequently seen in psoriasis in humans. These unusual regional and developmental effects of TGF-alpha suggest a natural role for the growth factor in (1) controlling epidermal thickness during development and differentiation, (2) involvement in papilloma formation, presumably in conjunction with TGF-beta, and (3) involvement in psoriasis, in conjunction with some as yet unidentified secondary stimulus stemming from mild mechanical irritation/bacterial infection.
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PMID:Transgenic mice provide new insights into the role of TGF-alpha during epidermal development and differentiation. 170 29

To investigate the histopathological characteristics of inverted papillomas of the urinary bladder, including the possibility of malignant transformation, we studied the indicators of cellular proliferation activity in 7 inverted papillomas of the bladder including two cases of malignant inverted papilloma of the bladder. PCNA expression rates in two cases of malignant inverted papilloma were higher than in benign inverted papillomas. Mean numbers of AgNORs per nucleus in malignant inverted papillomas were much more than in benign inverted papillomas. The c-erbB-2 oncoprotein was expressed only in malignant inverted papillomas. These results suggest that PCNA expression rate, mean number of AgNORs per nucleus and c-erB-2 oncoprotein expression may be merited as good indicators to detect the inverted papilloma with more proliferative and aggressive lesions, and with the potential of malignant transformation.
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PMID:Malignant inverted papilloma of the urinary bladder: the histopathological aspect of malignant potential of inverted papilloma. 757 90

Laryngeal papillomas are benign epithelial tumors caused by human papillomaviruses. These tumors are characterized by hyperplasia of the spinous layer and abnormal differentiation. Many tumor cell lines over-express the epidermal growth factor (EGF) receptor on their surface, and EGF regulates normal cell growth. We have asked about the relationship of the EGF receptor and EGF response in laryngeal papilloma cells. Papilloma cells showed markedly greater immunohistochemical staining for the EGF receptor, compared to uninfected cells. Both cell types showed a 2-3-fold increase in nuclei incorporating bromodeoxyuridine when EGF was present. Removal of EGF from papilloma cells cultured on collagen rafts permitted normal stratification and differentiation, as determined by synthesis of keratin 13. Inclusion of EGF induced abnormal differentiation with minimal expression of keratin 13. Uninfected laryngeal cells cultured on rafts in the presence of EGF synthesize keratin 13 in all suprabasal cells. EGF reduced both human papillomavirus RNA levels in the papilloma cells and expression of a reporter gene linked to the human papillomavirus 11 enhancers and E6 promoter in uninfected cells. These results suggest that the phenotype of papillomas is induced, in part, by EGF binding to the abundant EGF receptors.
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PMID:Laryngeal papilloma cells have high levels of epidermal growth factor receptor and respond to epidermal growth factor by a decrease in epithelial differentiation. 767 53

The levels of c-erbB-2 oncoprotein (ErbB-2 protein) in nipple discharge were evaluated together with those of carcinoembryonic antigen (CEA) in 9 patients with breast cancer, 2 patients with borderline lesions, 8 patients with intraductal papilloma, and 19 patients with fibrocystic change. When the tentative cutoff value was set at 40 ng/ml in the nipple discharge, elevated ErbB-2 protein levels were found in all 3 patients with palpable breast cancer and 3 of the 6 patients with nonpalpable cancer. Two of the 8 patients with intraductal papilloma had high ErbB-2 protein levels. A combination test with CEA resulted in positive detection in all cancer patients. Two patients with borderline lesions, 2 with intraductal papilloma and 2 with fibrocystic change were positive in a combination test. In addition, elevated ErbB-2 protein levels in nipple discharge correlated well with the overexpression of ErbB-2 protein in the tumor. All the patients with ErbB-2 protein levels over 100 ng/ml in their nipple discharge had comedo or solid intraductal carcinomas. Thus, measurement of ErbB-2 protein levels in nipple discharge can assist in the diagnosis of intraductal carcinoma and also in detecting tumors with a high proliferation rate and an overexpression of ErbB-2 protein: usually comedo or solid carcinomas.
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PMID:ErbB-2 protein levels in nipple discharge: role in diagnosis of early breast cancer. 790 88

The occurrence of different components of the cell growth regulation pathway as expressed in experimental skin carcinogenesis in haired carcinogen-sensitive NMRI, in haired carcinogen resistant DBA/2 mice and in hairless SKH/1 mice was studied by morphological and immunohistochemical methods. The results were compared with respect to neoplastic response, number of tumors, tumor behaviour and to the inducing agent (UV irradiation or chemical carcinogen), in order to increase our understanding of specific alterations in neoplastic development caused by extraneous agents and to determine their possible usefulness as indicators of carcinogen exposure. The expression of growth factors (transforming growth factor alpha and epidermal growth factor), growth factor receptors (epidermal growth factor receptor/c-erbB-1 and c-erbB-2/neu), cell signalling component c-myc, the nuclear transcription factor Harvey-Ras and the tumor suppressor gene p53, were studied in carcinogen- and UV-induced tumor formation in mouse. The results showed increased oncogene expression as well as growth factor expression in the skin during tumor development appearing early in neoplastic and premalignant conditions and becoming more distinct during neoplastic progression. Efforts to delineate specifically initiated cells prior to the appearance of morphologically detectable alterations including dysplasia, papilloma formation and squamous cell carcinomas, were unsuccessful. Increased staining by antibodies to growth factors and oncogenes were also observed in DBA/2 animals resistant to tumor formation. It is concluded that oncogene expression and growth factor protein deposits are associated with carcinogenic effects, partly explaining the mechanism of action of these agents, but the applicability, as such, for the analysis of potential hazardous agents needs further studies.
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PMID:Oncogenes and growth factors as indicators of carcinogen exposure. 867 68

The erbB-2 proto-oncogene belongs to a receptor tyrosine kinase family that includes the epidermal growth factor receptor, erbB-2, erbB-3, and erbB-4. erbB-2 is expressed in basal cells of the squamous epithelia and the outer root sheath of the hair follicles, but its function in epidermal development has not been well studied. To investigate its role in the skin, we created transgenic mice harboring an activated erbB-2 oncogene under the control of the human keratin 14 promoter. The keratin 14 promoter directed its expression to cells in which erbB-2 is normally expressed, whereas the activated receptor gene ensured increased signaling. All transgenic founder mice exhibited extensive and striking skin phenotype, including epidermal hyperplasia, preneoplasia, papilloma, hyperkeratosis, and dyskeratosis. The majority of the hair follicles were replaced by bizarre hyperproliferative intradermal squamous invaginations, whereas the rest of the follicles exhibited severe hyperplasia and disorganization. All but one of the transgenic mice died before or shortly after birth, probably as a consequence of defects in the skin and esophagus. These observations demonstrate that the skin is sensitive to erbB-2 signaling, suggesting an important role for this receptor tyrosine kinase in epidermal growth, differentiation, and hair follicle morphogenesis.
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PMID:Targeted expression of activated erbB-2 to the epidermis of transgenic mice elicits striking developmental abnormalities in the epidermis and hair follicles. 956 51

Clinical and epidemiological data have linked cervical cancer to the Human Papilloma Virus (HPV) infection. However, the presence of HPV infection alone is not enough to cause tumorigenesis, suggesting a role for additional host-cell genetic factors. The aim of the present work was to study the association of K-ras and c-erbB-2 mutations in cervical tissue samples with different grades of dysplasia and infected with HPV-6 ("low-risk" type) or HPV-16 and HPV-18 ("high-risk" types). Negative HPV-DNA samples were used as controls. The detection of K-ras and c-erbB-2 activation were performed by Artificial Refractory Mutation System (ARMS)-PCR and semiquantitative PCR, respectively. Statistical analysis showed a highly significant difference in K-ras codon 12 mutation frequency between high-risk and low-risk HPV-infected samples (p<0.05). On the other hand, amplification of the c-erbB-2 oncogene appeared associated to tissue samples infected with HPV-6 (p<0.003). Cervical carcinoma appears to arise from a series of well-characterized progressive histological changes, but the genetic alterations necessary for cervical tumorigenesis are not yet clear. These results raise the possibility for a role of certain proto-oncogenes and their activation in cervical neoplasia.
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PMID:Association between activated K-ras and c-erbB-2 oncogenes with "high-risk" and "low-risk" human papilloma virus types in preinvasive cervical lesions. 1094 49

C-erbB-2 oncoprotein (ErbB-2 protein)and carcinoembryonic antigen (CEA)were simultaneously evaluated in the breast cyst fluid of 6 patients with intracystic cancer, 6 patients with intracystic papilloma, and 42 patients with gross cystic disease. A combination test, using 12 ng of ErbB-2 protein and 150 ng of CEA/ml of cyst fluid, respectively, as cutoff values resulted in a positive detection rate of 83%(5/6 cases) for intracystic breast cancer. Two of the 6 patients with intracystic papilloma and 2 of the 42 patients with gross cystic disease were positive. In addition, elevated levels of these markers in cyst fluid correlated well with the expression of these antigens in the corresponding tumor. Thus, it can be concluded that measurements of ErbB-2 protein and CEA aid in the diagnosis of intracystic breast cancer, and the assay of ErbB-2 protein is valuable for detecting tumors in which this protein is overexpressed.
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PMID:Simultaneous Assay of ErbB-2 Protein and Carcinoembryonic Antigen in Cyst Fluid as an Aid in Diagnosing Cystic Lesions of the Breast. 1109 3

Recurrent respiratory papillomatosis (RRP) has a juvenile aggressive form and an adult more indolent form. Most cases of RRP are cytologically benign; however, some undergo malignant transformation. At present, there are no known markers that help identify patients at risk for aggressive disease. We investigated by immunohistochemistry expressions of topoisomerase alpha II, MIB-1, p53, p21, E-cadherin, retinoblastoma (RB) gene protein product, HER-2/neu, and steroid hormone receptors in a case of juvenile respiratory papillomatosis with malignant transformation to determine whether these markers are associated with malignant transformation. Histologic examination of the pulmonary lobectomy specimen revealed well-differentiated squamous carcinoma and invasive papillomatosis. Increased staining was found in areas of invasive papillomatosis for topoisomerase alpha II, p53, and MIB-1, with highest labeling indices in areas of squamous carcinoma. Staining intensity for RB gene protein product showed gradual decline from benign papilloma (3+) and invasive papillomatosis (2+) to squamous carcinoma (0-1+). Expression of p21 was similar in benign papilloma and invasive papillomatosis but showed reduction in squamous carcinoma. Expressions of E-cadherin, HER-2/neu, and steroid hormone receptors did not appear to correlate with biologic behavior. Increased topoisomerase alpha II and p53 expression along with reduced RB gene protein product and p21 expression may serve as markers of transformation to invasive papillomatosis and squamous carcinoma.
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PMID:Topoisomerase alpha II, retinoblastoma gene product, and p53: potential relationships with aggressive behavior and malignant transformation in recurrent respiratory papillomatosis. 1127 21


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