Varying patterns of expression of insulin-like growth factors I and their receptors in murine mammary adenocarcinomas of different metastasizing ability

F.K. GUERRA,; A.M. EIJÁN,; L. PURICELLI,; D.F. ALONSO,; E. BAL DE KIER JOFFE,; A. KORNBLIHTT,; E.H. CHARREAU,; P.V. ELIZALDE

INTERNATIONAL JOURNAL OF CANCER. JOURNAL INTERNATIONAL DU CANCER.

JOHN WILEY & SONS INC

Año: 1996 vol. 65 p. 1 - 10

0020-7136

20. Int J Cancer. 1996 Mar 15;65(6):812-20. Varying patterns of expression of insulin-like growth factors I and II and their receptors in murine mammary adenocarcinomas of different metastasizing ability. Guerra FK, Eijan AM, Puricelli L, Alonso DF, Bal de Kier Joffé E, Kornblihgtt AR,Charreau EH, Elizalde PV. Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina. We studied the expression of insulin-like growth factors I (IGF-I) and II(IGF-II) and their receptors (IGF-R) in 2 related murine mammary adenocarcinomain vivo lines, M3 and MM3, with different metastasizing ability. We furtherinvestigated the effects of IGFs on the secretion of a key enzyme in themetastatic cascade, the urokinase-type plasminogen activator (uPA) in M3 and MM3 cells. M3 is a spontaneous mammary tumor originated in BALB/c mice, with a 40%incidence of lung metastases. MM3 variant, obtained by successive s.c. implantsof M3 lung metastases into syngeneic mice, shows a 95% incidence of lungmetastases. Similar levels of expression of IGF-I protein were found in M3 andMM3 tumors, whereas IGF-II expression was 4-fold higher im MM3. RNAse protection assays showed similar levels of IGF-I mRNA in M3 and MM3 tumors and revealed a4-fold increase in IGF-II transcripts in MM3 tumors compared with M3. AuthenticIGF-I and II messages were also found in primary cultures of M3 and MM3 cells.IGF-I mRNA levels were similar in both cultures and, as described for solidtumors a 5-fold increase in IGF-II message was detected in MM3 cells. Thepresence of type I and mannose-6-phosphate (Man-6P)/type II IGF-R wasdemonstrated in both M3 and MM3 tumors. A 2-fold increase of type I IGF-R wasdetected in MM3 tumors compared with M3. Man-6P/type II IGF-R levels were 2-fold lower in MM3 tumors than in M3. As observed in tumor membranes, type I IGF-Rconcentrations were higher and Man-6P/type II IGF-R lower in cultures of MM3epithelial cells compared with MM3 cells. In addition, we found that IGF-Ienhanced secreted uPA activity in both M3 and MM3 cells while IGF-II onlystimulated uPA secretion in MM3 cells.  PMID: 8631597 [PubMed - indexed for MEDLINE]