Abstract
We describe here the expression pattern of the breast cell growthinhibitor Mammastatin in normal and breast cancer cells. Normal Cells (NHMC)over-express Mammastatin in low calcium media. Mammastatin has been isolatedfrom low calcium conditions to demonstrate that it is a tissue specific growthinhibitor. These studies demonstrate that Mammastatin is expressed as a 53 kD,growth inhibitory protein in 138/138 normal breast cell lysates and isexpressed as a 44 kD species without activity (where measured) in 28 of 41breast cancer cell lysates. Consistent differential expression of Mammastatinsuggests a negative role for Mammastatin in cellular transformation.
Highlights
Cancer has been shown to be a multi-varient disease that can becaused by many different factors
We describe here agrowth inhibitory protein that is consistently absent in breast cancer.Mammastatin, is expressed in 70% of breast cancers but is not expressed as the53 kD form identified in normal cells in any cell line or tissue lysate
Since itis possible that lack of a growth inhibitor may be involved in loss of growthcontrol, Mammastatin is being studied as a potential breast cancer therapy.These studies describe the expression patterns of Mammastatin in normal andtransformed mammary cells and in breast tissue derived from healthy women ascompared to breast cancer patients
Summary
Cancer has been shown to be a multi-varient disease that can becaused by many different factors. The most widely accepted cause for cancer isa mutation that interrupts the coding sequence of a critical growth controlgene in a manner that either activates a growth stimulatory pathway orinactivates a growth inhibitory pathway. In our view, both of these phenomenamust occur. The growth promoting mutations have been shown to span the signaltransduction pathway from external growth factor to cell cycle control genes.The growth restricting pathways are not as well understood. Asreported elsewhere the protein is expressed as an active, 53 kD, phosphorylatedprotein only in normal breast epithelial cells (in press). Our currentobservations of differential expression of the protein Mammastatin may provideinsight into the transformation process
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