Expression of functional prolactin and its receptor in human colorectal cancer.
OBJECTIVE
Ectopic production of prolactin has been reported for several tumors, and elevated prolactin plasma levels have been detected in colorectal cancer patients. However, the role of prolactin in colorectal cancer remains unclear. We therefore compared expression patterns of prolactin and its receptor in normal and neoplastic colonic mucosa of the same patient with noncancer controls and determined mitogenic effects in vitro.


METHODS
mRNA and protein expression was analyzed by semiquantitative RT-PCR and western blotting. Localization of ligand and receptor in tissues was investigated by immunohistochemistry. Mitogenic effects of prolactin on colorectal cancer cell lines (Caco-2, HT-29, LoVo) were assayed by [(3)H]thymidine incorporation.


RESULTS
mRNA expression of prolactin was detected in 13% of normal and 27% of cancer specimens, with the highest levels seen in moderately differentiated tumors. Receptor mRNA was amplified from the majority of normal (96%) and cancer (94%) samples with an overexpression seen in tumor tissues. Protein expression of prolactin was detected in cancer tissues only, with the highest levels seen in moderately differentiated tumors. Receptor protein expression was correlated with the RT-PCR data, showing up to fourfold overexpression in tumor tissues. Staining for both ligand and receptor was observed in epithelial cells. DNA synthesis was significantly stimulated by prolactin in all cell lines reaching 167-197% of unstimulated controls.


CONCLUSIONS
Expression of prolactin, overexpression of prolactin receptors in colorectal cancers, and mitogenic effects of prolactin suggest a role for this hormone in a subgroup of colorectal cancers, which is presumably mediated by paracrine/autocrine pathways.
Otte
Jan-Michel
JM
I. Department of Internal Medicine, Christian-Albrechts-Universität, Schittenhelmstrasse 12, 24105 Kiel, Germany.
Otte
Claudia
C
Beckedorf
Stefanie
S
Schmitz
Frank
F
Vonderhaar
Barbara K
BK
Fölsch
Ulrich R
UR
Kloehn
Sievert
S
Herzig
Karl-Heinz
KH
Mönig
Heiner
H
D000199:Actins / Q000378:metabolism; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011388:Prolactin / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011981:Receptors, Prolactin / Q000096:biosynthesis* / Q000235:genetics; D013223:Statistics as Topic; D014407:Tumor Cells, Cultured
D000199:Actins; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D011981:Receptors, Prolactin; D011388:Prolactin