GOLPH2 and MYO6: putative prostate cancer markers localized to the Golgi apparatus.
BACKGROUND
Malignant transformation is often accompanied by morphological and functional alterations in subcellular organelles. The Golgi apparatus is a subcellular structure primarily involved in modification and sorting of macromolecules for secretion and transport to other cellular destinations. Molecular alterations associated with the Golgi apparatus may take place during prostate carcinogenesis but such alterations have not been documented.


METHODS
To demonstrate that the Golgi apparatus undergoes alterations during prostate carcinogenesis, we examined the expression and localization of two candidate molecules, Golgi phosphoprotein 2 (GOLPH2) and myosin VI (MYO6), both overexpressed in prostate cancer as initially identified by expression microarray analysis.


RESULTS
Elevated GOLPH2 expression in prostate cancers was validated through real-time RT-PCR, Western blot, and tissue microarray analysis, and its Golgi localization in surgical prostate cancer tissues confirmed using two-color immunofluorescence. In addition, distinctive juxtanuclear MYO6 staining pattern consistent with Golgi localization was observed in surgical prostate cancer tissues. Two-color immunofluorescence revealed intensive Golgi-specific staining for both GOLPH2 and myosin VI in prostate cancer cells but not in the adjacent normal prostate epithelium.


CONCLUSIONS
We show that the Golgi apparatus in prostate cancer cells differs from the normal Golgi by elevated levels of two molecules, GOLPH2 and MYO6. These results for the first time demonstrated consistent cancer cell-specific alterations in the molecular composition of the Golgi apparatus. Such alterations can be explored for discovery of novel prostate cancer biomarkers through targeted organellar approaches.
Wei
Shuanzeng
S
Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Dunn
Thomas A
TA
Isaacs
William B
WB
De Marzo
Angelo M
AM
Luo
Jun
J
D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; C410824:GOLM1 protein, human; D008565:Membrane Proteins; C089785:myosin VI; D018995:Myosin Heavy Chains