EFFECT OF SIALOADENECTOMY ON MEDROXYPROGESTERONE-ACETATE-INDUCED MAMMARY CARCINOGENESIS IN BALB C MICE - CORRELATION BETWEEN HISTOLOGY AND EPIDERMAL-GROWTH-FACTOR RECEPTOR CONTENT/

To evaluate the possible involvement of the salivary glands in the mod ulation of medroxyprogesterone (MPA)-induced mammary tumorigenesis, 48 sialoadenectomized virgin BALB/c female mice and 47 controls were tre ated with 40mg MPA depot s.c. every 3 months for 1 year. Mammary tumor s developed in 11 sialoadenectomized and in 34 control mice with simil ar latencies. In both groups, 75% of the tumors were ductal and proges tin-dependent (PD) while the remainder were lobular and progestin-inde pendent (PI). Epidermal growth factor (EGF) levels were measured in sa livary glands (SG-EGF) and serum (S-EGF) in both groups. MPA induced a significant increase in SG-EGF an din S-EGF that became evident only after 1 month of MPA treatment. No increase in S-EGF was detected in M PA-treated sialoadenectomized mice, indicating that salivary glands ar e the major source of S-EGF. The presence of EGF receptors (EGF-R) was investigated in ductal PD and PI tumor line sand compared with 8 PI t umor lines of lobular origin. A significant difference in EGF-R conten t was found between lobular and ductal tumors. No increase in EGF-R wa s noted when ductal tumors became autonomous. EGF-R did not correlate with tumor growth rate and there was an inverse correlation between EG F-R and steroid receptors. When the effect of sialoadenectomy on tumor growth was tested in vivo in syngeneic transplants of 2 ductal PD, 1 ductal PI and 2 lobular PI mammary adenocarcinomas, it was not found t o be significant when compared with the controls. It may be concluded that SG-EGF plays an important role in the induction of mammary adenoc arcinomas by MPA, while it has no significant effect on the growth of established tumors. (C) 1994 Wiley-Liss, Inc.