Coordinate loss of growth regulatory factors following castration of rats carrying the Dunning R3327 G prostatic tumor.
Hormonal manipulation of prostate cancer is an effective therapy for metastatic disease. Unfortunately, following an initial response tumors reestablish themselves as hormone independent variants and progress. This study was designed to assess the interrelationship of cytokeratin P (Cyto P), vimentin, epidermal growth factor receptor (rEGF) and tissue testosterone following androgen deprivation therapy. Animals bearing the hormone dependent Dunning R3327 G subline prostatic adenocarcinoma were surgically castrated and progressing tumors from both hormone intact and castrated groups were quantitatively assayed for immunohistologic reactivity against the described markers. The results demonstrate a significant (p < 0.05) decrease in cytokeratin (Cyto P), rEGF and testosterone levels following castration. When the expression of both rEGF and Cyto P are related to the tissue testosterone content, it is observed that the ratio between rEGF and testosterone remains essentially unchanged (0.65 +/- 0.21 to 0.65 +/- 0.41), suggesting that in the Dunning R3327 G subline, rEGF expression is coordinately under androgen control. At least some cytokeratin expression also appears to be particularly sensitive to androgen levels, since the ratio between Cyto P and testosterone decreased from 0.92 +/- 0.39 to 0.35 +/- 0.41 following castration. In contrast, following castration, the expression of vimentin was unaffected.
Rubenstein
M
M
Division of Cellular Biology, Hektoen Institute for Medical Research, Chicago, Illinois.
Shaw
M
M
Targonski
P
P
McKiel
C F
CF
Dubin
A
A
Guinan
P D
PD
D000230:Adenocarcinoma / Q000378:metabolism / Q000601:surgery; D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007633:Keratins / Q000378:metabolism; D008297:Male; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000601:surgery*; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000601:surgery*; D051381:Rats; D013739:Testosterone / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
D007381:Intermediate Filament Proteins; D014746:Vimentin; D013739:Testosterone; D007633:Keratins; D066246:ErbB Receptors