The Ste20 kinase MST4 plays a role in prostate cancer progression.
MST4, a member of the Sterile 20 serine/threonine kinase family, was found to be expressed in prostate carcinoma tumor samples and cell lines. In addition, expression levels appeared to correlate with tumorigenicity and androgen receptor status of the cells. Ectopic expression of wild-type and kinase-inactive MST4 was used to alter cellular MST4 activity levels in three widely studied human prostate tumor cell lines: LNCaP, DU 145, and PC-3. Overexpression of wild-type MST4 induced anchorage-independent growth of the LNCaP cell line, and increased both in vitro proliferation and in vivo tumorigenesis of the DU 145 cell line. On the other hand, expression of a kinase-inactive form reverted the anchorage-independent growth phenotype and highly tumorigenic behavior of the PC-3 cell line. MST4 kinase activity was stimulated significantly by epidermal growth factor receptor ligands, which are known to promote growth of prostate cancer cells. Together, our studies suggest a potential role for MST4 in the signal transduction pathways involved in prostate cancer progression.
Sung
Victoria
V
SUGEN, Inc., South San Francisco, California 94080, USA.
Luo
Wen
W
Qian
Dapeng
D
Lee
Isabelle
I
Jallal
Bahija
B
Gishizky
Mikhail
M
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology / Q000556:secondary; D000328:Adult; D002448:Cell Adhesion; D002455:Cell Division; D018450:Disease Progression; D004790:Enzyme Induction; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009928:Organ Specificity; D011467:Prostate / Q000201:enzymology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000473:pathology; D000099317:Hippo Kinases
D004815:Epidermal Growth Factor; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins; C430908:STK26 protein, human; D000099317:Hippo Kinases