Expression of glycodelin in human breast and breast cancer.
Glycodelin is a 28 kDa glycoprotein with structural homology to beta-lactoglobulins, particularly expressed in steroid-responsive tissues of the female reproductive tract. We previously found that transfection of glycodelin cDNA into MCF-7 breast cancer cells induces differentiation into organized acinar epithelium and up-regulation of epithelial markers. In this study, we used immunohistochemistry, Northern blotting and reverse transcription-polymerase chain reaction (RT-PCR) analyses to study glycodelin expression in normal and in malignant breast tissues. The results were compared with the expression of estrogen (ER) and progesterone receptors (PR) and p53 tumor suppressor protein. Glycodelin was found in ductal and lobular epithelium of 6/6 normal breast tissues, 27/29 morphologically normal breast tissues from breast cancer patients, 6/6 benign lactating adenomas, 21/35 ductal carcinomas, 9/9 tubular carcinomas, 9/9 mucinous carcinomas, 3/3 mixed ductal/tubular carcinomas and 7/11 lobular carcinomas. In the latter, of particular interest was the presence of glycodelin in paranucleolar vacuoles of carcinoma cells. Northern blot analysis of fresh frozen tissues revealed the normal full length 0.9 kb mRNA of glycodelin in ductal breast carcinoma. Using RT-PCR analysis, glycodelin messenger ribonucleic acid was found in 13/13 ductal and in 3/3 tubular tumor tissues. We also detected a splicing variant lacking exon 4, which includes the nucleotide sequence encoding the potential N-glycosylation site at Asn-85. Our results demonstrate the synthesis of glycodelin in normal breast and breast cancer. In addition, we show that the paranuclear vacuole, characteristically present in lobular breast cancer cells, contains abundant amounts of glycodelin.
Kämäräinen
M
M
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
Halttunen
M
M
Koistinen
R
R
von Boguslawsky
K
K
von Smitten
K
K
Andersson
L C
LC
Seppälä
M
M
D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017398:Alternative Splicing; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D005091:Exons; D005260:Female; D014644:Genetic Variation; D000071816:Glycodelin; D006023:Glycoproteins / Q000032:analysis* / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D011257:Pregnancy Proteins / Q000032:analysis* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics; D011980:Receptors, Progesterone / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics
D000071816:Glycodelin; D006023:Glycoproteins; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53