Protein tyrosine kinase activity in 350 T1/T2, N0/N1 breast cancer. Preliminary results.
Protein tyrosine kinases (PTKs) are a family of enzymes sharing a highly conserved catalytic domain which phosphorylates substrate proteins on tyrosine residues. PTKs play a major role in the transduction of the mitogenic signal and are involved in the control of cell proliferation, differentiation, and transformation processes. PTKs can be subdivided into two major types: membrane associated PTKs consisting essentially of growth factor receptors (receptor tyrosine kinases or RTKs) and cytosolic PTKs involved in the intracellular transduction of mitogenic and differentiation signals. From January 1988 to January 1992, PTK activity was assayed in cytosolic fractions prepared from 350 T1-T2, N0-N1 M0, breast carcinomas. Enzymatic activity was measured using phosphate transfer from [32P]-ATP to poly-Glu-Tyr as an artificial substrate. According to our previously reported pilot study, we chose a cut-off value of 12 pmol 32P incorporated min-1 mg-1 protein, corresponding to the median value. We found positive PTK levels (> or = 12 pmol/min/mg) to be correlated with a loss of differentiation according to Scarff-Bloom grade (p < 0.001), negative PR (p = 0.03) and ER status (p = 0.04). With a median follow-up of 30 months (0-82), patients with a positive PTK level presented a smaller 3-year disease free survival than in the PTK negative group of patients (p = 0.07). In Cox multivariate analysis including pT, pN, Scarff-Bloom grade, PR and ER, PTK activity does not emerge as a significant prognostic factor.
Bolla
M
M
Biochemistry Department, CHU A. Michallon, Grenoble, France.
Rostaing-Puissant
B
B
Bottari
S P
SP
Chedin
M
M
Marron-Charriere
J
J
Colonna
M
M
Berland
E
E
Chambaz
E
E
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
D011505:Protein-Tyrosine Kinases