Expression of cytokeratin messenger RNA versus protein in the normal mammary gland and in breast cancer

Abstract

It is not known how tightly regulation of cytokeratin (CK) protein expression is correlated with transcriptional activity in breast cancer. The level of control of CK expression in the normal mammary gland and in breast cancer has been assessed by combining in situ hybridization with riboprobes, and with immunohistochemistry using monospecific antibodies. In normal mammary gland, luminal cells showed abundant hybridization with complementary RNA (cRNA) probes for CK7, CK8, CK18, and CK19. Proteins of these CKs were correspondingly distributed except for that of CK19, which showed a heterogeneous staining. In primary carcinomas, both messenger RNAs (mRNAs) and proteins of CK8 and CK18 were generally expressed to a degree similar to that of normal epithelia, but a lower level of mRNA and protein of CK18 was observed in metastatic carcinomas. Reduced expression of CK7 and CK14 was observed in all carcinomas, and the correlation between mRNA and protein for these two cytokeratins was unbalanced, whereas the expression of CK19 mRNA and the proportion of its protein-positive cells were increased. The results suggest that these major CKs in normal mammary gland epithelia are regulated at the transcriptional level except for CK19, which is partially under the posttranscriptional control. The alterations observed in breast cancer are not only reflected by the reduced or increased expression of individual cytokeratins, but characterized by partial loss of the normal regulation of cytokeratin expression.