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Insulin-like Growth Factor Binding Proteins in Human Breast Cancer Tissue¹

Minerva Institute for Medical Research, 00250 Helsinki [F. P.]; Medix Research Unit, 00250 Helsinki [T. N.]; Department of Pathology, University of Helsinki 00290 Helsinki [V. I.]; and Department of Pathology, Jorvi Hospital, 02740 Espoo [S. P.], Finland

Breast tumor cell lines have been shown to secrete at least five distinct insulin-like growth factor (IGF) binding proteins (IGFBP), the secretion being related to the estrogen receptor (ER) content. In this study we investigated IGFBP mRNA expression and IGFBP content in relation to ER content in human breast tumors. Tissue specimens from 47 breast cancers were studied. In five cases the adjacent histologically normal tissue was also analyzed. IGFBP content in tissue homogenates was studied by Western ligand blot analysis, using [¹²⁵I] IGF-I as a label, and IGFBP mRNA expression by reverse transcriptase polymerase chain reaction. The results show that human breast tumors express mRNAs encoding IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4 and IGFBP-5. The pattern of IGFBPs in different tumors varies. No correlation exists between ER content and IGFBPs with molecular weights 24,000 Mr, 28,000 Mr, 34,000 Mr or 43,000 Mr, whereas the 49,000 Mr IGFBP was more abundant in ER negative tumors (P < 0.05). The IGFBP content was significantly (P < 0.05) higher in five tumors than in their adjacent normal tissues suggesting that increased content of IGFBPs is a feature typically associated with the malignant transformation of breast tissue.

¹ This work was supported by grants from the Sigrid Jusélius Foundation, Finnish Cancer Association, Nordiska Insulinfonden, Finsk-Norsk Stiftelse and Livoch Hälsa.

² To whom requests for reprints should be addressed, at Minerva Institute for Medical Research, Tukholmankatu 2, 00250 Helsinki, Finland.

Received 2/ 3/92. Accepted 7/20/92.

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