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)

Estra-1,3,5 (10)-triene-3,17-diol (17 beta)-, 3-[bis(2-chloroethyl) carbamate] (Estramustine EM) was tested for its anticancer effect on human endometrial cancer cell lines: Ishikawa and its estrogen (E) independent sub-clone EIIL (Estrogen Independent Ishikawa Line). The results showed: (1) EM inhibited growth of both cell lines in a dose dependent manner giving ID50 for Ishikawa as 12 microM and for EIIL as 65 microM. (2) The addition of EM to the culture medium caused cell detachment and death associated with a breakdown of DNA to approximately 90 base pair fragments. (3) Reverse transcription-polymerase chain reaction to examine expressions of c-erbB-2, nidogen and fas showed that EM completely abolished fas expression and resulted in a 40% decrease in nidogen expression in Ishikawa but not in EIIL. No change was seen in c-erbB-2 expression. The present data indicate that the E component of EM does not stimulate the growth of Ishikawa or EIIL. Since the growth of both cell lines was inhibited but apparently in an E receptor (ER) dependent manner, EM may be of value in an adjuvant therapy for endometrial cancer, especially an ER positive one.
 ...
PMID:[Estramustine phosphate, estrogen conjugated with nitrogen mustard inhibits the growth of endometrial cancer cells in vitro]. 777 15

Tumor cells traverse the basement membrane zone and gain access to the underlying mesenchyme to eventually form metastases. Laminin 5 is a major component of the basement membrane and connects keratinocytes at the level of hemidesmosomes to the mesenchyme. Underneath invading tumor cells anti-laminin 5 staining is diminished, and laminin 5 degradation products can stimulate cell migration and epidermal growth factor (EGF) receptor signaling. To investigate laminin 5 expression in parental HaCaT and tumorigenic c-Ha-ras-transformed HaCaT II-4rt keratinocytes, the cells were cultivated under monolayer and organotypic culture conditions. In monolayer cultures, HaCaT and c-Ha-ras-transformed HaCaT II-4rt keratinocytes secreted comparable amounts of laminin 5. After 7 days of organotypic cultures, collagen IV, beta4-integrin, nidogen and laminin 5 were detected along the epithelial-mesenchymal interface of parental HaCaT keratinocytes, while staining for these proteins was patchy or absent in the organotypic cultures with c-Ha-ras-transformed HaCaT II-4rt cells. Immunoblotting analysis confirmed absence of laminin 5 deposition in organotypic cultures of c-Ha-ras-transformed HaCaT II-4rt while the protein was detected in organotypic cultures of HaCaT keratinocytes. Surprisingly, however, the alpha3 and gamma2 laminin chain transcripts were strongly induced in c-Ha-ras-transformed HaCaT II-4rt cells by organotypic culture conditions, indicating that invasive epidermal tumor cells retain high mRNA levels for laminin 5 chains and suggesting an autocrine/paracrine induction of the laminin chain mRNAs. Moreover, as laminin 5 was absent in organotypic cultures of c-Ha-ras-transformed HaCaT II-4rt cells, it suggests immediate degradation of the protein. Degradation products may further contribute to the malignant phenotype by enhancing cellular migration and EGF-receptor activation.
 ...
PMID:Expression of laminin 5 by parental and c-Ha-ras-transformed HaCaT keratinocytes in organotypic cultures. 1646 Aug 39