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William L Gerald

Publications and source records attributed to William L Gerald.

39 records · Page 3Linked to original sources

High expression of the Met receptor in prostate cancer metastasis to bone.

OBJECTIVES: Expression of the active Met receptor tyrosine kinase causes tumor metastasis in animal models. To begin to analyze whether Met expression might be related to the spread of prostate cancer cells, we investigated whether its expression correlates with prostate-specific antigen recurrence and whether its expression depends on the site of metastasis. METHODS: Ninety radical prostatectomy specimens with a Gleason sum of 6 or 7 and 86 specimens of bone, lymph node, and soft-tissue metastasis were immunohistochemically stained for Met, and a semiquantitative scoring system for Met in heterogeneously positive prostate cancers was applied. Met protein in prostate cancer cell lines was measured by Western blotting. RESULTS: With the exception of two lymph node metastases, all metastases and 51% of the primary prostate cancers expressed Met. Moreover, the bone metastases expressed significantly more Met than did the lymph node metastases. However, in prostate cancer with a Gleason sum of 6 or 7, Met was not a prognostic marker for prostate-specific antigen recurrence. In prostate cancer cell lines, Met expression correlated inversely with expression of the androgen receptor. CONCLUSIONS: The high expression of the Met receptor tyrosine kinase in bone metastasis renders Met a promising target for nuclear imaging and treatment of metastatic prostate cancer.

Bone Neoplasms↗

Induction of BAIAP3 by the EWS-WT1 chimeric fusion implicates regulated exocytosis in tumorigenesis.

Desmoplastic small round cell tumor (DSRCT) is defined genetically by the chimeric fusion of the Ewing's sarcoma and Wilms' tumor genes, generating a novel transcription factor, EWS-WT1. By using cells with inducible EWS-WT1 to screen high-density microarrays, we identified BAIAP3 as a transcriptional target of the chimera. The BAIAP3 promoter is specifically bound in vivo by the (-KTS) isoform of EWS-WT1, consistent with its activation in reporter assays. BAIAP3 encodes a protein implicated in regulated exocytosis, which is colocalized with a secreted growth factor within cytoplasmic organelles. Ectopic expression of BAIAP3 in tumor cells dramatically enhances growth in low serum and colony formation in soft agar. BAIAP3 therefore encodes a transcriptional target of an oncogenic fusion protein that implicates the regulated exocytotic pathway in cancer cell proliferation.

Angiogenesis Inhibitors↗