Normanno N, Qi C, Gullick W, Persico G, Yarden Y, Wen D, Plowman G, Kenney N, Johnson G, Kim N, Brandt R, Martinezlacaci I, Dickson R, Salomon D
NCI,TUMOR GROWTH FACTOR SECT,TUMOR IMMUNOL & BIOL LAB,BLDG 10,BETHESDA,MD 20892. HAMMERSMITH HOSP,IMPERIAL CANC RES FUND,MOLEC ONCOL LAB,LONDON W12 0HS,ENGLAND. INT INST GENET & BIOPHYS,I-80125 NAPLES,ITALY. WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. AMGEN INC,THOUSAND OAKS,CA 91320. BRISTOL MYERS SQUIBB CO,INST PHARMACEUT,SEATTLE,WA 98121. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. GEORGETOWN UNIV,LOMBARDI CANC RES CTR,WASHINGTON,DC.
Int J Oncol. 1993 Jun;2(6):903-11. doi: 10.3892/ijo.2.6.903.
Cripto-1 (CR-1), amphiregulin (AR), and heregulin alpha (HRGalpha) are three recently discovered epidermal growth factor (EGF)-related peptides. The expression of these proteins was determined in MCF-7, ZR-75-1, T-47D, SK-BR-3, MDA-MB-231, MDA-MB-468, and Hs-578T human breast cancer cell lines using reverse transcriptase-polymerase chain reaction (RT-PCR), Northern blotting, and immunocytochemistry (ICC). The expression of CR-1 mRNA was detected by RT-PCR in all of the breast cancer cell lines. AR mRNA was detected by Northern blot analysis in MCF-7, ZR-75-1, T-47D, MDA-MB-231, and MDA-MB-468 cells while HRGalpha mRNA was expressed in only MDA-MB-231 and Hs-578T cells. All estrogen receptor-positive cell lines were found to express AR mRNA, and estrogen was able to induce AR mRNA expression in estrogen-depleted MCF-7 cells. CR-1 and AR proteins could be immunocytochemically detected in the breast cancer cell lines that were expressing CR-1 and AR mRNA using monospecific rabbit polyclonal antibodies. The anti-CR-1 antibody was also used to examine 26 human primary breast carcinomas by ICC for CR-1 expression. Seventy-five percent of the carcinomas were found to express the CR-1 protein while the adjacent non-involved breast epithelium was negative. These data demonstrate that CR-1, AR, and HRGalpha are coexpressed in human breast cancer cells and suggest that these three EGF-related peptides might perform a role in the autocrine growth regulation of human breast carcinoma cells.
