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)

We have studied epidermal growth factor (EGF) receptor expression in endometrium and in endometriotic implants, testing a group of 36 women before and after a 4-month gonadotropin-releasing hormone (GnRH) analog (GnRH-a) goserelin depot treatment. Each woman underwent laparoscopy twice. At the initial laparoscopy, before starting treatment, the disease was staged according to the American Fertility Society (AFS) classification and biopsies of endometriotic implants were undertaken. The follow-up laparoscopy was performed within 5 weeks of the last GnRH-a administration. Biopsies were taken from areas of previously noted disease, both visually persistent and visually free of disease. At the time of each laparoscopy, photographs of all areas of disease were taken. Specimens of eutopic endometrium were collected from each patient at the time of laparoscopy by a Novak curette. Endometrial and endometriotic samples were processed for immunohistochemical detection of EGF receptor, using anti-EGF receptor monoclonal antibody Ab-3. After treatment, the marked improvement of AFS score was associated with a dramatic reduction of EGF receptor immunostaining, but the exact meaning of this finding is still not completely understood. The dramatic reduction of EGF receptor expression in eutopic and ectopic endometrium samples after treatment is not obviously related to the hypoestrogenism induced by the drug. It has been suggested that steroid hormones and EGF play a role in regulation of EGF receptor expression, so that drugs such as goserelin depot could act directly at local peripheral level influencing the EGF receptor expression via the production of its ligand.
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PMID:Influence of goserelin depot therapy on epidermal growth factor receptor expression in pelvic endometriosis. 908 34

TTF-1 is a member of the Nkx family of homeodomain genes required for morphogenesis of the hypothalamus. Whether TTF-1, or other Nkx genes, contributes to regulating differentiated hypothalamic functions is not known. We now report that postnatal hypothalamic TTF-1 expression is developmentally regulated and associated with the neuroendocrine process of female sexual development. Lesions of the hypothalamus that cause sexual precocity transiently activate neuronal TTF-1 expression near the lesion site. In intact animals, hypothalamic TTF-1 mRNA content also increases transiently, preceding the initiation of puberty. Postnatal expression of the TTF-1 gene was limited to subsets of hypothalamic neurons, including LHRH neurons, which control sexual maturation, and preproenkephalinergic neurons of the lateroventromedial nucleus of the basal hypothalamus, which restrain sexual maturation and facilitate reproductive behavior. TTF-1 mRNA was also detected in astrocytes of the median eminence and ependymal/subependymal cells of the third ventricle, where it colocalized with erbB-2, a receptor involved in facilitating sexual development. TTF-1 binds to and transactivates the erbB-2 and LHRH promoters, but represses transcription of the preproenkephalin gene. The singular increase in hypothalamic TTF-1 gene expression that precedes the initiation of puberty, its highly specific pattern of cellular expression, and its transcriptional actions on genes directly involved in neuroendocrine reproductive regulation suggest that TTF-1 may represent one of the controlling factors that set in motion early events underlying the central activation of mammalian puberty.
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PMID:TTF-1, a homeodomain gene required for diencephalic morphogenesis, is postnatally expressed in the neuroendocrine brain in a developmentally regulated and cell-specific fashion. 1116 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.
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PMID:Clinical and experimental progression of a new model of human prostate cancer and therapeutic approach. 1148 33