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

The MCF10AT premalignant human breast epithelial cells form benign ductal structures in immunodeficient mice which sporadically progress to carcinoma in situ and invasive cancers of different histologic types. MCF10CA1 cell lines are malignant variants derived by serially passing small pieces of tumors in athymic mice before establishing cells in culture. As these MCF10CA1 variants gave rise to heterogeneous tumors, some cell lines were cloned. Inoculated into immunodeficient mice, these variants produce squamous carcinomas with an undifferentiated component or adenocarcinomas also with an undifferentiated component. Immunohistochemistry utilized antibodies against DF3, c-erbB-2, cyclin Dl, m keratin, p keratin, p53, B72.3 and estrogen receptor. We detected characteristic patterns for squamous carcinomas, for adenocarcinomas, and for each undifferentiated component, that is the undifferentiated components of the squamous and glandular carcinomas were distinct. Only adenocarcinomas were focally ER positive. One uncloned variant that produced cancers with a glandular component, MCF10CA1h, was cloned and cells were injected into mice. This clone produced only undifferentiated carcinomas that, compared to tumors formed by the parental uncloned variant, had lost ER, DF3 and c-erbB-2 expression, but more strongly expressed p53. Our data demonstrate the potential of the premalignant MCF10AT model to generate heterogeneity, including both estrogen receptor-positive as well as estrogen receptor-negative tumors, during progression.
 ...
PMID:Progression of premalignant MCF10AT generates heterogeneous malignant variants with characteristic histologic types and immunohistochemical markers. 1120 Jul 73

We report the clinical evolution of a prostate cancer, metastasizing to lungs and bones, recurring locally, and escaping from anti-androgen therapy. Key event of biological progression of the patient's tumor was the coincidence of allelic imbalance accumulation and of bone metastases occurrence. The recurrent tumor was established as the transplantable xenograft PAC120 in nude mice, where it grew locally. PAC120 displayed the same immunophenotype of the original tumor (positive for keratin, vimentin, prostatic acid phosphatase, and Leu-7) and expressed human HOXB9, HOXA4, HER-2/neu, and prostate-specific antigen genes, as detected by reverse transcriptase-polymerase chain reaction. It formed lung micrometastases detected by mRNA expression of human genes. Cytogenetic analysis demonstrated numerous alterations reflecting the tumor evolution. PAC120 was still hormone-dependent; its growth was strongly inhibited by the new gonadotropin-releasing hormone antagonist FE 200486 but weakly by gonadotropin-releasing hormone superagonist D-Trp(6)-luteinizing-hormone releasing hormone (decapeptyl). Tumor growth inhibition induced by anti-hormone therapy was linked to the hormone deprivation degree, more important and more stable with FE 200486 than with D-Trp(6)-luteinizing-hormone releasing hormone. Surgical castration of mice led to tumor regressions but did not prevent late recurrences. Transition to hormone-independent tumors was frequently associated with a mucoid differentiation or with a neuroendocrine-like pattern. Independent variations of mRNA expression of HER-2/neu and prostate-specific antigen were observed in hormone-independent tumors whereas HOXB9 gene expression was constant. In conclusion, PAC120 xenograft, a new model of hormone-dependent prostate cancer retained the progression potential of the original tumor, opening the opportunity to study the hormone dependence escape mechanism.
 ...
PMID:Clinical and experimental progression of a new model of human prostate cancer and therapeutic approach. 1148 33

Keratin intermediate filaments are heteropolymers composed of type I and type II keratins. Ultraviolet B (UVB) irradiation induces keratin expression by keratinocytes. Using SV40-transformed human keratinocytes (SVHK), we investigated the effect of UVB irradiation on keratin expression. UVB irradiation (10 mJ/cm(2)) increased keratin 5 and keratin 14 mRNAs and proteins without affecting cell viability. Upregulation of keratin 5 and keratin 14 was dependent on the dose of radiation: the effect was observed at 5 mJ/cm(2) and the maximal effect was observed at 10 mJ/cm(2). Higher UVB doses (more than 10 mJ/cm(2)) were cytotoxic. Expression of keratin 1 and keratin 10 was marginal in SVHK and was not affected at either the mRNA or protein level by UVB. The stimulatory effects on keratin 5 and keratin 14 expression were also observed in cultured normal human keratinocytes (NHK) and HaCaT keratinocytes. The tyrosine kinase inhibitor, genistein, and the epidermal growth factor (EGF) receptor inhibitor, AG1429, significantly suppressed the increase in expression of keratin 5 and keratin 14 by SVHK. In contrast, the suppressive effect was not observed with the protein kinase C inhibitor, H-7. Furthermore, pretreatment with neutralizing anti-EGF receptor antibody also suppressed UVB-induced keratin 5 and keratin 14 expression by SVHK, NHK and HaCaT cells. UVB irradiation did not affect the steady-state expression of TGF-alpha by SVHK. Immunoprecipitation and immunohistochemical studies revealed that UVB irradiation induced EGF receptor activation in the absence of EGF and TGF-alpha. These results indicate that UVB increases keratin 5 and keratin 14 expression through direct activation of the EGF receptor in SVHK.
 ...
PMID:Ultraviolet B irradiation increases keratin 5 and keratin 14 expression through epidermal growth factor receptor of SV40-transformed human keratinocytes. 1187 47

Atypical adenomatous hyperplasia (AAH) of the prostate is a microscopic proliferation of small acini that may be mistaken for adenocarcinoma. Although some data suggest that AAH is associated with adenocarcinoma arising in the transition zone, the clinical significance of this lesion is uncertain. Therefore we studied the DNA ploidy pattern and immunophenotype of AAH as compared with nodular hyperplasia and well-differentiated adenocarcinoma in 23 formalin-fixed, paraffin-embedded, whole-mounted retropubic prostatectomies. Representative sections were immunostained for keratin 34beta-E12, chromogranin, bcl-2, c-erbB-2, ki67-MIB1, and factor VIII (microvessel density). DNA ploidy was determined by image analysis and Feulgen-stained sections. There were rare scattered immunoreactive cells for chromogranin, bcl-2, and c-erbB-2 in nodular hyperplasia and AAH (mainly in the basal cell compartment) and in carcinoma. The ki67-MIB1 labeling index was different between nodular hyperplasia and AAH (p<0.001) and carcinoma (p=0.003) but not between AAH and carcinoma (p=0.203). Microvessel density was different between AAH and carcinoma (p=0.001) but not between nodular hyperplasia and AAH (p=0.105) or carcinoma (p=0.0820). All foci of nodular hyperplasia, AAH, and carcinoma were diploid. Ploidy status and our selected panel of antibodies did not discriminate among these 3 entities reliably.
 ...
PMID:Atypical adenomatous hyperplasia (adenosis) of the prostate: DNA ploidy analysis and immunophenotype. 1586 80

The presence of keratin granulomas in peritoneal cavity associated with ovarian endometrioid carcinoma, which might be related to leakage from the ovarian tumor, is rarely reported. Its clinical significance has not yet been well investigated. We report a case presenting with intermittent abdominal pain after an acute episode 1 month before a complex adnexal tumor was noted. Comprehensive cytoreductive surgery was performed. The ovarian tumor was an endometrioid adenocarcinoma with squamous differentiation. There were diffuse brownish flecks over the omental surface and pelvic peritoneum, which contained fragments of degenerated squamous cells, keratin, and numerous foreign body giant cells. Extensive multiple sections were examined for these implants. DNA flow cytometry and various immunostaining studies (HER-2/neu, p53, CK-7, and cytokeratin [AE1/AE3]) were performed. Since viable epithelial cells in the implants could be differentially identified against mesothelial or granulomatous components by CK-7 staining and DNA aneuploidy was demonstrated on primary ovarian tumor, four courses of chemotherapy were administered. The patient has been free of disease for 18 months since diagnosis.
 ...
PMID:Ovarian endometrioid carcinoma with diffuse pigmented peritoneal keratin granulomas: a case report and review of the literature. 1644 70

Mechanical stretching represents an important part of the signaling in skin. We have previously demonstrated that mechanical stretching induced proliferative phenotypes in human keratinocytes, as shown in increased 5-bromo-2'-deoxyuridine (BrdU) incorporation, ERK1/2 activation, and keratin K6 induction. Here we have further investigated the antiapoptotic signals in human keratinocytes provoked by mechanical stretching in vitro. Keratinocytes were plated on flexible silicone supports to transmit mechanical stretching to keratinocytes, involving continuous stretching by +20%. Stretching of these cells for 15-30 min caused the phosphorylation and activation of Akt. Inhibition of mitogen and extracellular signal-regulated kinase (MEK1/2) with U0126 and phosphoinositide 3-OH kinase (PI 3-K) with Wortmannin attenuated Akt activation. The epidermal growth factor (EGF) receptor kinase inhibitor, AG1478, and calcium channel inhibitor, gadolinium (Gd3+), also inhibited Akt activation. In summary, our results demonstrate the activation of the Akt signaling pathway by mechanical stretching, generating not only proliferative but also antiapoptotic signals in human keratinocytes.
 ...
PMID:Activation of Akt by mechanical stretching in human epidermal keratinocytes. 1663 75


<< Previous 1 2