Role of Pregnancy Specific Glycoproteins in Breast Cancer Development
Final rept. 9 Aug 97-8 Aug 98
HENRY M JACKSON FOUNDATION ROCKVILLE MD
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Pregnancy specific glycoproteins PSGs are secreted proteins of unknown function that belong to the carcinoembryonic antigen gene family CEA. CEA is a commonly used tumor marker for adenocarcinomas. Expression of PSGs in normal breast tissue is undetectable by current techniques but they have been shown to be expressed in certain tumors including breast ductal and lobular carcinomas by immunohystochemistry. Because polyclonal anti-PSG antibodies can cross react with other members of the CEA family, we have examined the expression of PSGs by reverse transcriptase-polymerase chain reaction with PSG-specific primers. Our results indicate that all 8 breast cancer cell lines expressed mRNA encoding for PSGs and their splice variants. When breast tumors were examined, 29 out of 89 tumors expressed PSGs. When we looked at the different PSGs expressed in these tumors, we found that they all expressed PSG 4 and some other PSG. Several splice variants were detected some of which may have been previously undetected in placental tissue. We have produced one recombinant PSG containing the integrin binding motif RGD, and one lacking the RGD tripeptide in insect cells. These proteins were produced as fusions with glutathione-S-transferase and have the predicted molecular mass. These proteins were used in studies to determine if they have any effect in cell proliferation of a breast cancer line. No effects in cell proliferation were detected and our binding studies indicated that they most likely do not express receptors in the cells that produce them.
- Medicine and Medical Research