Table 1.

Summary of homeobox gene expression and function in mammary gland development and neoplasia

Gene	Gene	Expression		Expression altered in		Mammary or in vitro
family	namea	detected inb:	Methodc	neoplasias ?	Possible regulation?	phenotype?	Reference
Hox/HOX	Hoxa-1	MG (UD)	RT-PCR; Northern	OE (freq.)	Extracellular matrix		[31*,33*]
		Scp2, CID-9			components
	HOXA-1	MCF7	RT-PCR		Retinoic acid		[63,30]
	Hoxa-5	CID-9	RT-PCR				[33*]
	Hoxa-7	MG	RT-PCR				[31*]
	HOXA-7	MG	RT-PCR				1
	Hoxa-9	MG	RT-PCR			KO: lactational defects	[38*]
	HOXA-10	MCF7	RT-PCR		Vitamin D	OE in MCF7: promotes cell cycle	[30,64]
						arrest at G1
	Hoxb-6	MG	RT-PCR; Northern	Lost			[31*]
	HOXB-6	MCF7	RT-PCR				[30]
	Hoxb-7	MG (E+S)	Northern; in situ	UE	Extracellular matrix	OE in SkBr3 cells: bFGF induction;	[33*,57]
					components; developmental	increased proliferation; decreased
						growth factor dependency
	Hoxb-8	CID-9	RT-PCR				[33*]
	Hoxb-9	CID-9 E12.5	RT-PCR; in situ			KO: lactational defects	[33*,38]
		Embryo (MM)
	Hoxc-6	MG	Northern	Lost	Estrogen (-); developmental		[31]
	HOXC-6	MCF7; MCF7D;	cDNA screen;		Variable		[57,65]
		Hs578Bst;	RT-PCR
		MCF10F; T47D
	Hoxc-8	MG	Northern	Lost	Estrogen (-); developmental		[32]
	HOXC-10	MG	PCR of cDNA library				2
	Hoxd-3	MG (UD)	Northern	OE (rarely)			[32]
	Hoxd-4	MG (E)	In situ	Lost			[32]
	Hoxd-8	MG	Northern	Lost	Developmental		[32]
	Hoxd-9	MG (E+S);	RT-PCR;	Lost	Developmental	KO: lactational defects	[32,38]
		E12.5 Embryo	Northern; in situ
		(MM)
	Hoxd-10	MG (E+S)	Northern; in situ	Lost	Developmental	KO: lactational defects	[32,39];2
	Hoxd-11	MG (UD)	Northern	No			[32]
	Hord-12	MG	RT-PCR;	OE (myc tumor)			[31*]
			Northern (UD)
Msx	Msx-1	E13.5 Embryo (E);	Northern; in situ	Maintained but variable	Developmental	KO: none detected in embryos	[40*,41*]
		MG (E)
	Msx-2	E13.5 Embryo (E);	Northern; in situ	Lost	Estrogen; developmental	KO: MG fail to form	[40*];3
		MG (S)
Iroquois related	IRX-1	MG	RT-PCR				[48*]
	IRx-2	MG; primary	RT-PCR; Northern;	Maintained, expression	Developmental		[48*]
		tumors	in situ	levels or splice form
				usage may be altered
				in some tumors
	IRX-3	MG	RT-PCR				[48*]
	IRX-4	MG	RT-PCR				[48*]
	IRX-5	MG	RT-PCR				[48*]
Paired domain	Alx-4	MG(S)	In situ		Expression associated with	KO: none detected	[45]
					actively condensing periductal
					stroma
HSIX	HSIX-1	MCF7		OE	Expressed in S phase	OE in MCF7 abolishes X-ray induced	[58*]
					of cell cycle	cell cycle arrest in G2 phase
POU domain	OCT-1	MCF7; MCF10;	RT-PCR;				[54]
		SkBr3;MDA-	Western EMSA
		MB453
	Oct-1	MG (lact.)	RT-PCR				[53]
	OCT-2	MCF7; MCF10;
		SkBr3	RT-PCR;				[54]
			Western EMSA
	OCT-3	MG (UD); MCF7;	RT-PCR	OE (freq.)		Form with a 5 amino acid deletion	[54]
		MCF10; SkBr3;				detected om MCF7 cell
		primary tumors
	Oct-3	MG (lact.)	RT-PCR				[53]
	OCT-11	MG (UD) MCF7;	RT-PCR; EMSA	OE (freq.)			[54]
		skBr3; MDA-
		MB453; primary
		tumors
	Pit-rs 1	MG (lact.)	RT-PCR				[53]
	Pou4f1 = Brn-3	MG (lact.)	RT-PCR				[53]
	Pou4f-rs1 =	MG (lact.)	RT-PCR				[53]
	Brn-3R
	Pou3f4 = Brn-4	MG (lact.)	RT-PCR				[53]
	Pou3f-rs1 =	MG (lact.)	RT-PCR				[53]
	POU-IIIA
Engrailed related	En-1	MG	Northern	UE (freq.)	Developmental		[32]
	En-2	MG (UD)	Northern	UD		KO: none detechted	[32]
MOX	MOX1	MG					[52]
MEIS	MEIS2a	MG	RT-PCR of cDNA library				4
	MEIS 2d	MG	RT-PCR of cDNA library				4
	MRG1a	MG	RT-PCR of cDNA library				4

bFGF, basic fibroblast growth factor; E, epithelium; EMSA, electrophoretic mobility shift assay; freq., frequently; KO, knockout mutation; lact., lactating; M, mammary mesenchyme; MG mammary gland; Northern, Northern blot assay; OE, overexpressed; RT-PCR, reverse transcriptase polymerase chain rection; S, periductal stroma; UD, undetectable; UE, underexpressed. ^aHuman genes are uppercase; mouse genes are lowercase. ^bCalle lines are listed by their common designation. If expression was detected in the intact mammary gland, the tissue compartment is shown. ^cNot all detection techniques have been used on all tissue types/cell lines shown. ¹Friedmann Y, Daniel CW, unpublished results; ²Lewis MT, Daniel CW, unpublished results; ³Maas R, unpublished results, cited in [41]; ⁴Lewis MT, unpublished results.