title: Premenopausal Obesity and Breast Cancer Growth Rates in a Rodent Model.
abstract: Obese premenopausal women with breast cancer have poorer prognosis for long term survival, in part because their tumors are larger at the time of diagnosis than are found in normal weight women. Whether larger tumor mass is due to obesity-related barriers to detection or to effects on tumor biology is not known. This study used polygenic models for obesity and breast cancer to deconstruct this question with the objective of determining whether cell autonomous mechanisms contribute to the link between obesity and breast cancer burden. Assessment of the growth rates of 259 chemically induced mammary carcinomas from rats sensitive to dietary induced obesity (DS) and of 143 carcinomas from rats resistant (DR) to dietary induced obesity revealed that tumors in DS rats grew 1.8 times faster than in DR rats. This difference may be attributed to alterations in cell cycle machinery that permit more rapid tumor cell accumulation. DS tumors displayed protein expression patterns consistent with reduced G1/S checkpoint inhibition and a higher threshold of factors required for execution of the apoptotic cell death pathway. These mechanistic insights identify regulatory targets for life style modifications or pharmacological interventions designed to disrupt the linkage between obesity and tumor burden.
authors.affiliation: Cancer Prevention Laboratory, Colorado State University, Fort Collins, CO 80523, USA. shawna.matthews@ucdenver.edu.
authors.forename: Shawna B
authors.initials: SB
authors.lastname: Matthews
authors.affiliation: Cancer Prevention Laboratory, Colorado State University, Fort Collins, CO 80523, USA. john.mcginley@colostate.edu.
authors.forename: John N
authors.initials: JN
authors.lastname: McGinley
authors.affiliation: Cancer Prevention Laboratory, Colorado State University, Fort Collins, CO 80523, USA. elizabeth.neil@colostate.edu.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Neil
authors.affiliation: Cancer Prevention Laboratory, Colorado State University, Fort Collins, CO 80523, USA. henry.thompson@colostate.edu.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Thompson
mesh_terms: D050154:Adiposity; D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D049109:Cell Proliferation; D004041:Dietary Fats / Q000009:adverse effects*; D005260:Female; D015994:Incidence; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced* / Q000150:complications; D015999:Multivariate Analysis; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000150:complications; D009765:Obesity / Q000150:complications*; D051381:Rats; D012307:Risk Factors; D047368:Tumor Burden
chemical_list: D004041:Dietary Fats
keywords: apoptosis; breast cancer; cell proliferation; obesity; premenopausal; tumor growth