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 modulation of medroxyprogesterone (MPA)‐induced mammary tumorigenesis, 48 sialoadenectomized virgin BALB/c female mice and 47 controls were treated with 40mg MPA depot s.c. every 3 months for 1 year. Mammary tumors developed in 11 sialoadenectomized and in 34 control mice with similar latencies. In both groups, 75% of the tumors were ductal and progestin‐dependent (PD) while the remainder were lobular and progestin‐independent (PI). Epidermal growth factor (EGF) levels were measured in salivary glands (SG‐EGF) and serum (S‐EGF) in both groups. MPA induced a significant increase in SG‐EGF and in S‐EGF that became evident only after 1 month of MPA treatment. No increase in S‐EGF was detected in MPA‐treated sialoadenectomized mice, indicating that salivary glands are the major source of S‐EGF. The presence of EGF receptors (EGF‐R) was investigated in ductal PD and PI tumor lines and compared with 8 PI tumor lines of lobular origin. A significant difference in EGF‐R content was found between lobular and ductal tumors. No increase in EGF‐R was noted when ductal tumors became autonomous. EGF‐R did not correlate with tumor growth rate and there was an inverse correlation between EGF‐R and steroid receptors. When the effect of sialoadenectomy on tumor growth was tested in vivo in syngeneic transplants of 2 ductal PD, I ductal PI and 2 lobular PI mammary adenocarcinomas, it was not found to be significant when compared with the controls. It may be concluded that SG‐EGF plays an important role in the induction of mammary adenocarcinomas by MPA, while it has no significant effect on the growth of established tumors.