Biology of Somatostatin and Somatostatin Receptors in Breast Cancer.
Annual rept. 12 Aug 97-11 Aug 98
MCGILL UNIV MONTREAL (QUEBEC)
Pagination or Media Count:
Fifty additional primary human breast tumor samples were analysed for SSTR1-5 mRNA and shown to be all receptor positive. Mean SSTR mRNA level was the highest for SSTR3 followed by SSTR1, SSTR2, SSTR5, and SSTR4. Statistical analysis showed a negative correlation between SSTR2 and tumor size, a positive correlation between SSTR2 and estrogen receptors ER, and a trend towards a positive correlation between SSTR2 and progesterone receptor, SSTR1 and ER, SSTR1 and lymph node status, and SSTR3 and tumor grade. Breast cancer cell lines also expressed multiple SSTR subtypes but the level of receptor expression was less than that in solid tumors. A panel of antibodies against hSSTR1-5 was produced which detected all five SSTR antigens by Western blots and immunocytochemistry. Both analyses showed a correlation between receptor subtype expression at the protein level with SSTR mRNA levels. All five SSTRs inhibited tumor cell growth, SSTR3 by triggering apoptosis, and the remaining four subtypes by inducing cytostasis SSTR5 SSTR2 SSTR4 SSTR1. Both cytostatic and cytotoxic signalling were dependent on G protein-linked activation of phospho-tyrosine phosphatase SHP1. SSTR3-induced apoptosis led to induction of wt p53, an increase in Bax, and activation of a cation insensitive acidic endonuclease. Cytostasis involved dephosphorylation and activation of pRb and activation of the CDK inhibitor 21. The C-terminal domain of hSSTR5 is crucial for its cytostatic signalling.
- Anatomy and Physiology
- Medicine and Medical Research