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)

Short term explant cultures of benign prostatic hyperplasia (BPH) tissues were studied immunohistochemically to characterise both the morphological changes within the explant tissue and the cellular origin of the epithelial cell outgrowth. Altered patterns of expression of cytokeratins, prostate specific antigen (PSA) prostatic acid phosphatase (PAP), and epidermal growth factor (EGF) receptor were observed. After sloughing of the secretory epithelium in the majority of the acini repopulation and outgrowth of a monolayer was accomplished by cells which were strongly positive for stratifying keratin and EGF receptor and negative for PAP and PSA, indicative of a basal cell phenotype. The peak of proliferation in the acini, as assessed by Ki-67 immunohistochemistry, occurred after 2-4 days in culture. Preliminary studies on BPH tissue xenografts in nude mice indicated that better preservation of normal morphology, secretory activity, and antigen expression could be achieved.
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PMID:Studies on the proliferation, secretory activities, and epidermal growth factor receptor expression in benign prostatic hyperplasia explant cultures. 137 29

Primary and metastatic tumor tissues of serous papillary adenocarcinoma of the endometrium were examined for the following: (1) amplification of int-2, c-erbB-2 and c-myc proto-oncogenes by Southern blot hybridization; (2) DNA ploidy by flow cytometric study; (3) and expression of specific proteins, such as estrogen and progesterone receptors, keratin, vimentin, and carcinoembryonic antigen (CEA) using immunohistochemical and biochemical techniques. Amplification of c-myc was observed in the specimens from the endometrium (ten-fold) and from omental metastasis (five-fold). Both int-2 and c-erbB-2 amplification were not observed. The tumor showed aneuploidy, with the specimens from the endometrium and omental metastasis exhibiting multiple populations of aneuploid tumor cells. Estrogen and progesterone receptors could not be detected biochemically; however, immunohistochemically, estrogen receptors were observed in tumor cells forming papillary structures but not in the tumor cells of the solid, more poorly differentiated areas. A similar distribution was observed for both low and high molecular weight keratin. The findings of c-myc amplification and aneuploidy in the serous papillary adenocarcinoma of the endometrium are consistent with its aggressive behavior observed clinically and emphasize the importance of distinguishing this lesion from other types of endometrial carcinoma.
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PMID:Serous papillary adenocarcinoma of the endometrium. Analysis of proto-oncogene amplification, flow cytometry, estrogen and progesterone receptors, and immunohistochemistry. 169 76

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

We have examined the character and carcinogenic properties of the normal-appearing epidermis overlying basal cell carcinomas by immunohistochemical methods, employing a series of monoclonal antibodies. The labelling index was significantly increased in the atrophic epidermis overlying basal cell carcinomas (solid type, n = 20), compared with the epidermis overlying or adjacent to squamous cell carcinoma (n = 20), keratoacanthoma (n = 10), dermatofibroma (n = 10), neurofibroma (n = 10), soft fibroma (n = 10), pyogenic granuloma (n = 10) and cutaneous leiomyoma (n = 5). Cells which expressed epidermal growth factor (EGF) receptor were detected in all layers of the epidermis over the basal cell carcinomas, but not the other tumours. Basement membrane-related antigens, including bullous pemphigoid antigen and GB3 antigen, were decreased in the epidermis. AE1, the monoclonal antibody against basal cell keratin, reacted with the uppermost layers of the normal-appearing epidermis overlying the basal cell carcinomas. ICAM-1 expression was very weak in the overlying epidermis. The dermis subjacent to the proliferating epidermis showed staining for transforming growth factor-alpha (TGF-alpha), strong positive PECAM-1 staining of endothelium, and numerous HLA-DR-positive cells. From these results, we suggest that the proliferative activity in the epidermis overlying basal cell carcinomas is not a state induced by the dermal infiltrate, but represents carcinogenic activity of the epidermis.
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PMID:Immunohistochemical evaluation of epidermis overlying basal cell carcinomas. 768 54

Cervical cancer is not considered a hormone-responsive tumor in spite of the presence of estrogen receptors (ER) and progesterone receptors (PgR) in some of them. Endocrine treatments have not achieved clinical responses, however, tamoxifen has been reported to induce PgR and to inhibit cell growth of many cervical carcinoma cell lines. In this study we investigated whether tamoxifen administration affects the histopathological characteristics of cervical cancer and the expression of ER, PgR, HER-2/neu and p53 protein. Nineteen patients with invasive cervical cancer free of previous treatments were studied. The triphenylethylene antiestrogen tamoxifen was given orally during 10 days (20 or 40 mg/day). Pre- and post-tamoxifen biopsies were evaluated using slides stained with hematoxylin and eosin and immunostained (ER, PgR, HER-2/neu, p53, PCNA, keratin, heat shock protein 27,000 daltons). Estrogen receptors were present in 37% and PgR in 16% of the biopsies from untreated patients. Only one case that was PgR-negative before tamoxifen administration showed weak PgR-positivity following antiestrogen administration. No obvious changes were observed in ER, HER-2/neu and p53 proteins. A statistically significant decrease in the number of mitotic figures was obtained in 16% (3/19) of the post-tamoxifen biopsies and two of them showed higher differentiation. The results showed that tamoxifen did not induce changes in estrogen-regulated proteins in cervical cancer. However, the data showed that certain cervical carcinomas had changes in their proliferation and differentiation levels following tamoxifen administration. These findings suggest that tamoxifen may affect some cervical cancer tissues by a hormone-independent mechanism(s).
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PMID:Effects of short-term tamoxifen administration in patients with invasive cervical carcinoma. 790 50

We recently described culture conditions that allow proliferation of metastatic human breast cancer cells from biopsy specimens of certain patient samples. These conditions resulted in the development of an immortalized cell strain designated SUM-44PE. These same culture conditions were used to isolate a human breast cancer cell strain from a metastatic lymph node of a separate breast cancer patient. The SUM-16LN human breast cancer cells isolated from this specimen were cultured either in serum-free medium or serum-containing medium supplemented with insulin and hydrocortisone. Unlike the SUM-44PE cells that have proliferated in culture continuously for over two years, SUM-16LN cells proliferated in culture for approximately 200 days and underwent 15 to 20 population doublings before undergoing cell senescence. No cells of this strain proliferated beyond passage 8. SUM-16LN cells were keratin-19 positive and had an aneuploid karyotype. These cells overexpressed p53 protein and had an amplified epidermal growth factor (EGF) receptor gene that resulted in high level expression of tyrosine phosphorylated EGF receptor protein. Despite the presence of high levels of tyrosine phosphorylated EGF receptor in these cells, they proliferated in serum-free, EGF-free medium and did not secrete detectable levels of EGF-like mitogenic growth factor. In addition, these cells were potently growth inhibited by all concentrations of exogenous EGF tested and by the neutralizing EGF receptor antibody Mab 425. These results suggest that the high level of tyrosine phosphorylated EGF receptor present in these cells is the direct result of receptor overexpression and not the result of the presence of a stimulatory ligand. Thus, SUM-16LN represents a human breast cancer cell strain that exhibited genetic and cellular characteristics of advanced human breast cancer cells. Nevertheless, these cells exhibited a finite proliferative lifespan in culture, suggesting that cellular immortalization is not a phenotype expressed by all human breast cancer cells.
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PMID:Finite proliferative lifespan in vitro of a human breast cancer cell strain isolated from a metastatic lymph node. 801 55

The present studies were aimed at determining if the use of a cell culture medium that supports proliferation of human mammary epithelial cells of the luminal lineage would allow routine isolation of breast cancer cells from primary and metastatic tumor specimens. Results obtained with mammary epithelial cells derived from reduction mammoplasty specimens and primary breast carcinomas indicated that growth of cells on type I collagen-coated dishes in Ham's F-12 medium supplemented with insulin, hydrocortisone, epidermal growth factor, cholera toxin, and 5% fetal bovine serum resulted in the growth and serial passage of cells that stained positively for the luminal cell marker cytokeratin 19. By contrast, growth of mammary epithelial cells in a growth factor-supplemented serum-free medium resulted in the emergence of mammary epithelial cell colonies that were uniformly negative for keratin 19. Filter isolation methods were used to isolate individual keratin-19-positive colonies from primary cultures derived from breast cancer specimens. All of the luminal mammary epithelial cells isolated from breast cancer tissues expressed characteristics of normal cells. Keratin-19-positive colonies isolated from several different tumors all grew rapidly for 30 to 60 days in culture and then senesced. Cells were isolated from one tumor that was known to have undergone a loss of heterozygosity at a specific locus in the p53 gene. All colonies isolated from this specimen contained both p53 alleles, which was consistent with their origin from normal luminal cells. Cells were also isolated from one tumor in which the c-erbB2 protein was drastically overexpressed in the neoplastic cells. Once again, keratin-19-positive colonies isolated from this tumor did not overexpress the c-erbB-2 protein. Experiments were then performed with cells derived from pleural effusions and metastatic lymph nodes. Results obtained with these specimens indicated that the growth conditions that support the growth of normal luminal mammary epithelial cells do not support the growth of neoplastic cells. However, the omission of cholera toxin, epidermal growth factor, and type I collagen substratum resulted in the isolation of two long-term cell lines. Both cell lines have population doubling times of approximately 100 h, are hyperdiploid, and stain positively for cytokeratin 19. Thus, culture conditions that support the growth of normal luminal mammary epithelial cells do not, in general, support the growth of breast cancer cells.
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PMID:Differential isolation of normal luminal mammary epithelial cells and breast cancer cells from primary and metastatic sites using selective media. 842 98

The activated neu (HER2/c-erbB-2) oncogene is extremely potent in inducing mammary cancer. For example, neu induces greater than 200 times as many tumors as the activated ras oncogene when directly introduced into in situ rat mammary epithelial cells using replication-defective retroviral vectors. In order to characterize mechanisms underlying this potency, we sought to identify uniquely overexpressed genes in neu-initiated tumors that were not overexpressed in tumors induced by weaker initiating agents, including activated ras and the chemical carcinogens dimethylbenz[a]anthracene and N-nitroso-N-methylurea. Several genes, including those encoding keratin K7 and the u haplotype of MHC class I RT1-A, were found to be overexpressed in neu-initiated carcinomas as well as in mammary carcinomas induced by other agents, when compared to their expression in normal mammary tissue. One gene, however, encoding a member of the lipocalin and calycin protein families, was 12-fold overexpressed in neu mammary tumors and was not overexpressed in ras or chemically induced carcinomas. This uniquely overexpressed gene was termed neu-related lipocalin (NRL). NRL protein was produced in a baculovirus system, purified and used to generate polyclonal antibodies. Western blot analysis indicate that neu-initiated mammary carcinomas express abundant NRL protein when compared to other mammary tumors.
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PMID:Overexpression of neu-related lipocalin (NRL) in neu-initiated but not ras or chemically initiated rat mammary carcinomas. 857 Jan 73

Hybrid tumours of the salivary glands are very rare entities composed of two different tumours, each of which conforms with an exactly defined category. We describe an unusual hybrid carcinoma of the palate; it was comprised of an adenoid cystic carcinoma and a salivary duct carcinoma with a transitional region. These two different compartments showed different characteristics as regards cellular differentiation, proliferative activity, and expression of oncogene and tumour suppressor oncogene proteins, as revealed by using markers for muscle actin, keratin, vimentin, S-100 protein, GFAP, Ki-67, p53, and c-erbB-2 proteins. This case is the first reported with overexpression of p53 and c-erbB-2 proteins in the tumour entities. Salivary gland tumours consist of heterogeneous histological groups, and each has morphological diversity. This case indicates that some of the oncogene and tumour suppressor oncogene proteins may help to produce the histological heterogeneity of the salivary gland tumour.
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PMID:A hybrid carcinoma: adenoid cystic carcinoma and salivary duct carcinoma of the salivary gland. An immunohistochemical study. 923 Sep 15

Analysis of growth factors and receptors in putative premalignant lesions of prostatic adenocarcinoma should aid our understanding of their growth pathways. Sixty prostatic TURP (transurethral resection of the prostate) specimens exhibiting atypical adenomatous hyperplasia (AAH) and/or prostatic intraepithelial neoplasia (PIN) lesions were assayed by immunohistochemistry for androgen receptor (AR), epidermal growth factor receptor (EGFR), c-erbB-2, transforming growth factor-alpha (TGF-alpha), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), MIB-1, E-cadherin, and high molecular weight keratin. Expression of these factors in the lesions was compared with that in the co-existing benign prostatic hyperplasia (BPH) or prostatic adenocarcinoma. Strong AR nuclear staining was observed in the luminal cells, but not the basal cells, of BPH and PIN lesions and in all the carcinomas examined. A similar growth factor and receptor profile was demonstrated in the secretory epithelium of high-grade PIN and carcinoma with a tendency to higher expression of membranous EGFR and c-erbB-2 and cytoplasmic TGF-alpha, and lower levels of FGF-2 than in low-grade PIN or BPH glands. Also, increased rates of proliferation, as estimated by MIB-1 stained cells, were observed in high-grade PIN in comparison with low-grade PIN and BPH and were not confined to the basal layer. AAH lesions resembled neither BPH nor carcinoma. Proliferation was virtually absent (MIB-1 expression); both AR and E-cadherin expression was significantly reduced; and, with the exception of FGF-2, all the other growth factors and receptors studied were absent. The results presented would support a premalignant role for high-grade PIN, whilst AAH would appear to represent a quiescent phenotype unlikely to progress to neoplasia.
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PMID:Expression of androgen receptor and growth factors in premalignant lesions of the prostate. 992 33


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