Enhanced expression of heregulin in c-erb B-2 and c-Ha-ras transformed mouse and human mammary epithelial cells.
Heregulin beta 1 was found to stimulate the anchorage-dependent, serum-free growth of nontransformed human MCF-10A mammary epithelial cells. Unlike epidermal growth factor, transforming growth factor alpha, or amphiregulin, heregulin beta 1 was also able to induce the anchorage-independent growth of MCF-10A cells. In contrast, the anchorage-independent, serum-free growth of c-Ha-ras or c-erb B-2 transformed MCF-10A cells was unaffected by heregulin beta 1, whereas heregulin beta 1 was able to stimulate the anchorage-independent growth of these cells. c-Ha-ras or c-erb B-2 (c-neu) transformed MCF-10A or mouse NOG-8 mammary epithelial cells express elevated levels of 2.5, 5.0, 6.5, 6.8, and 8.5 kb heregulin mRNA transcripts and/or synthesize cell-associated 25, 29, 50, and 115 kDa isoforms of heregulin. Since the MCF-10A cells and transformants also express c-erb B-3, these data suggest that endogenous heregulin might function as an autocrine growth factor for Ha-ras or erb B-2 transformed mammary epithelial cells.
Mincione
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Istituto di Patologia Umana e Medicina Sociale, Facoltà di Medicina e Chirurgia, Università D'Annunzio, Chieti, Italy.
Bianco
C
C
Kannan
S
S
Colletta
G
G
Ciardiello
F
F
Sliwkowski
M
M
Yarden
Y
Y
Normanno
N
N
Pramaggiore
A
A
Kim
N
N
Salomon
D S
DS
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002461:Cell Line, Transformed; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D018815:Genes, erbB; D011905:Genes, ras; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D020890:Neuregulin-1; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis
D002352:Carrier Proteins; D006023:Glycoproteins; D020890:Neuregulin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; C087230:heregulin beta1