ABSTRACT
Two different insulin-like growth-factor (IGF)-binding proteins have been found in human blood, one of high molecular mass and dependent on growth hormone for synthesis, the other of low molecular mass and independent of growth hormone. The small IGF-binding protein is abundant in human amniotic fluid. Its amino acid sequence has now been determined by direct analysis of the protein and its proteolytic fragments. Also, by immunoscreening a partial cDNA clone was isolated from a human hepatoma cell line. The mature protein consists of 234 amino acids and is coded for by an mRNA of approximately 1700 nucleotides in length. The primary structure of the protein reveals 18 Cys residues in N-terminal and C-terminal clusters and an Arg-Gly-Asp peptide sequence, common to extracellular proteins binding to receptors of the integrin family. A protein-sequence polymorphism was detected at position Ile/Met-228, indicating possible allelic variation. The 3'-untranslated mRNA sequence has a high A + T content and shows five copies of an ATTTA sequence, which has been shown to be involved in the regulation of the stability of certain mRNAs coding for growth-regulating proteins.
Subject(s)
Carrier Proteins/genetics , Cloning, Molecular , DNA/genetics , Amino Acid Sequence , Base Sequence , Carrier Proteins/blood , Cell Line , Chromatography, High Pressure Liquid , Humans , Insulin-Like Growth Factor Binding Proteins , Molecular Sequence Data , Molecular Weight , Peptide Fragments/isolation & purificationABSTRACT
The predictive value of nuclear DNA content in breast cancer in relation to clinical and morphologic factors was studied in 227 consecutive cases of invasive breast adenocarcinomas with follow-up periods of 8 to 13 years. The results show that, with the use of Cox multivariate analysis nuclear DNA content provided significant prognostic information additional to that given by all other clinical and histomorphologic variables taken together. This fact indicates that the DNA content of breast cancer cells reflects biological properties, associated with the malignant behavior of the tumor, other than those determining the stage of the disease. Nuclear DNA content was strongly correlated to histopathologic grading of the ductal carcinomas, with poorly differentiated tumors more likely to be aneuploid. On the other hand, no clear correlation was found to exist between nuclear DNA content and axillary node status, indicating that these two factors are independent prognostic parameters. It is noteworthy that DNA content provided additional prognostic information within both the node-negative and node-positive patient groups. In summary, the results shown here indicate that nuclear DNA content, as an objective biological marker of tumor aggressiveness, can significantly improve our prognostic capabilities within the currently designated stages.
